VOLUME: 22 - ISSUE: JAN 2016 |

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Inside this issue

3 News Uptoday 35 New Guidance 41 Audit Findings 42 Warning Letters

- Warning letter: Sun Pharmaceutical Industries Ltd. - Warning letter: One Way Drug, LLC - Warning letter: Thomas S. Tooma, M.D.

46 EU Non Compliance Report

- Non Compliance Report: Iason Italia SRL, Italy - Non Compliance Report: AstraZeneca Pharma India Ltd., India

49 Regulations of the Month

- Sec. 211.48 Plumbing (b) - Sec. 211.50 Sewage and refuse - Sec. 211.52 Washing and toilet facilities - Sec. 211.56 Sanitation (a)

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News Uptoday

Sanofi, AstraZeneca Collaborate to Share 210,000 Compounds

Sanofi and AstraZeneca are touting an innovative, open model of collaboration that will see the

direct exchange of 210,000 compounds between the two companies‘ proprietary libraries.

Announced in late November, the deal gives both companies free access to each other‘s usually

closely guarded compounds. Each company is free to develop any of the shared compounds without

any financial obligation and without restrictions on targeted disease areas.

The collaboration will enhance the chemical diversity of the compound collections and allow them to

screen a broader, more diverse chemical group as the starting point in developing new small-

molecule drugs.

The exchanged compounds specifically were selected to play off differences from their own current

libraries, the companies say. They will be exchanged in large enough quantities to enable the

receiving company to carry out high throughput screening for several years to determine if they are

active against a certain target. If a compound matches a target, it then can be modified to optimize

its structure before being classified as a ―lead compound‖ and entering development.

Even though the drugmakers work in similar disease areas like oncology, there is little chance that

they would develop similar drugs even using the same compound, because the companies have

different R&D methods.

This is a unique agreement, as large pharmaceutical companies typically seek to expand their

pipelines by licensing drugs from smaller biotech firms, or just buying them outright. AstraZeneca

also has struck compound sharing agreements with smaller companies, but nothing at this scale with

a major player like Sanofi.

MHRA to phase out submissions for medicines licences on physical media

Submissions on physical media (CD/DVD) for medicines licences will not be accepted by MHRA

from 1 February 2016.

Recently, MHRA concluded a period of consultation with all appropriate trade bodies about MHRA

plans to phase out the acceptance of regulatory submissions on physical media (CD/DVD).

As a result of our findings and in the absence of unresolved objections, MHRA will no longer accept

submissions on physical media from 1 February 2016.

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Source: https://www.gov.uk/government/news/mhra-to-phase-out-regulatory-submissions-for-

medicines-on-physical-media

Exporters demand to enhance validity of WHO GMP certificate from 2 to 3 years

The pharmaceutical exporters have demanded to enhance the validity period of World Health

Organization - Good Manufacturing Practices (WHO GMP) certificate from 2 years to 3 years from

the date of final inspection and recommendation to licensing authority as the exporters hardly get

one year time for registration since the time needed for Certificate of Pharmaceutical Product (CoPP)

and inclusion of new products takes more than six months.

The registration of product in every country takes minimum 16 to 18 months including countries in

Africa and Asia. Hence by the time registration documents are processed and come under

evaluation by respective drug authority, the CoPPs get expired. In such cases, the exporters are

again forced to obtain new CoPP legalisation which takes more time, additional expenses and delay

in registration. Also, most of the regulatory authorities are not accepting the CoPP with less than 6

months validity. Hence practically with the present two years' validity of GMP the exporters are able

to use it only for 18 months.

Currently, the validity of WHO GMP certification is given for 2 years only. All the importing countries

irrespective of size now takes minimum 2 years for product registration hence CoPP validity is

always a big problem and hurdle since by the time registration is on verge of completion CoPP gets

expired so for a fresh CoPP it takes at least 2 to 3 months time which further delays registration

period.

The exporters have therefore suggested that WHO GMP certificate should be issued for 3 years

from the date of final inspection and recommendation to licensing authority. Every Indian

manufacturer requires grant of WHO GMP certificate registration in order to export their

pharmaceutical preparations to different countries. CoPP is granted after joint inspections of the

manufacturing facilities by CDSCO officials and the state regulatory authorities. The validity of this

CoPP is for 2 years only. Re-inspection is required to get the new CoPP, but many a times re-

inspection is not possible in time due to various constraints and hence an extension of CoPP is

sought.

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Regulatory authorities in most countries do not accept CoPP with remaining validity of only 6

months. This means that CoPP is effectively valid only for 18 months. An extension of 6 months is

given, but only after the completion of 2 years validity which is of no significant value and the

registration process gets held up. The product registration offered by all countries is valid for 5 years.

The drug manufacturing license in India is also valid for 5 years. Hence it was urged that the validity

period of CoPP may also be 5 years or at least 3 years. This will help to expedite the registration of

products and in-turn will help boost the nation‘s pharmaceutical exports.

MHRA gives troubled Wockhardt plant all clear to manufacture for UK

Wockhardt has received a GMP certificate from the UK‟s MHRA for its facility in Chikalthana,

India.

The contractor announced the certificate in a statement filed with the Bombay Stock

Exchange yesterday.

“The Company has undergone recently an inspection at its L1-Chikalthana, Aurangabad

manufacturing facility by UK MHRA and have received a communication confirming the closure of

the inspection and issuance of an unrestricted GMP certificate,” the firm said.

This was confirmed with the European database of GMP compliance, which shows the certificate,

was issued on November 27, six weeks after the MHRA inspection which at the time Wockhardt said

resulted in no critical observations.

The plant – which makes generic drugs and antibiotics – has previously been the subject of

considerable regulatory criticism.

In October 2013 it was banned from exporting products to the UK after the country‘s Medicines and

Healthcare Products Regulatory Agency (MHRA) issued a certificate of non-compliance due to

cGMP violations.

A month after the MHRA‘s original suspension, the plant was hit by the US Food and Drug

Administration (FDA) which issued an import alert in November 2013 , banning exports of all but five

essential medicines made at the site.

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ManKind plans to build manufacturing plant in the Himalayas

ManKind Pharma plans to set up manufacturing facilities in Northeast India to bring

production in-house and cut its tax bill.

The Delhi company, which is not to be confused with US inhaled insulin developer MannKind

Corporation, will spend INR2bn ($30m) on new manufacturing facilities in India in 2016.

One of the new plants – which will make finished dosage forms for the Indian market – will be

constructed at an as yet unchosen site in Sikkim, a mountainous State in the North West of the

country that borders Nepal and Tibet.

Sikkim is popular with drugmakers despite the logistical challenges associated with running facilities

in the Himalayas.

Under State law, manufacturers that set up in the region before April 2017 will not have to pay taxes

on revenues generated by products made there for 10 consecutive years.

ManKind‘s plant is scheduled to be operational next March. The firm will join Cipla, Sun Pharma,

Zydus Cadila, Alembic, IPCA, Alkem Lab, Intas Pharma, Torrent Pharma and Unichem which all

have manufacturing operations in the State.

The second new ManKind facility – which is expected to open next summer – will be built at a site in

Behror in Rajasthan. The Indian drugmaker plans to make a range of active pharmaceutical

ingredients at the facility (API).

„Over 90%‟ of industry thinks Pfizer will sell generics biz

Pfizer says it will decide in 2018 whether to split its generics and branded businesses but

M&A experts are already predicting how the giant will get rid of its established drugs

programme.

Following news of the Pfizer-Allergan merger, the pharma world is united in predicting a split,

according to analyst Mark Schoenebaum, whose company Evercore ISI surveyed 448 industry

insiders and found more than 90% believe Pfizer ―should split eventually.‖

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Chrisoph Bieri, an M&A advisor to the pharma industry, backed up this claim. He told us mid-to-large

pharma is increasingly specialising to survive, and the biggest players are choosing either low-cost

generics, or shedding their off-brand portfolios to become originator specialists.

Just as Allergan in July sold to Teva the generics programmes it had amassed after mergers with

Actuis and Watson, Bieri predicts Pfizer is likely to do the same.

―We know that Pfizer also has a number of products off-patent and is trying to find a way to manage

them. We hear now that Pfizer is considering selling all the Pfizer generic drugs – perhaps via a

spin-off […] to focus on originator strategy.‖

Pfizer‘s previous generics policy was to try to commercialise what it calls its ―established products‖

programme through the same channels as original drugs. It then tried to split generics and branded

pharma within each country – ―that didn’t work either,‖ says Bieri.

―The latest we heard is they tried to build an established products unit, the same as Novartis.

Novartis have their generics drugs business [Sandoz] clearly separated – it’s clearly far away, even

geographically. You cannot mix your generics business – it’s a disaster.‖

On the market – but who wants to buy?

As for who Pfizer might sell its generics to, Bieri said there are few large generics players currently

who might want to take up the offer. Teva, Sandoz and Mylan are the current biggest off-patent

manufacturers.

He suggested it ―could make sense‖ for Sanofi and Pfizer to merge their generics businesses into a

new company, as Novartis and GSK funnelled their over-the-counter units in 2014 into a ―Consumer

Healthcare‖ joint venture.

Another question is ―whether Pfizer would sell Hospira [so soon after acquiring it] – it wouldn’t make

a lot of sense,‖ says Bieri. ―Hospira is niche – with sterile injectibles.‖

What is a „generic‟? Changing views

Talk of splitting big pharma between old and new drugs brings up some questions about terminology

– what counts as an originator drug these days? Small changes and add-ons intended to extend IP –

such as new formulations or different dosages of an existing API – are ―not reimbursed any more as

an original drug in Europe,‖ says Bieri. ―They look at it as a generic.‖

Regulators are likely to become stricter in their definitions for new drug submissions, he predicted:

―We assume that over time, having a new drug will mean a new chemical entity or biological entity.‖

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New Online submission system launched by CDSCO for clinical trials

New online submission system for clinical trials has been launched by Central Drugs Standard

Control Organization (CDSCO) in order to increase transparency, accountability and efficiency in

processing clinical trial applications.

The online submission system was launched due to decline in clinical trial applications and

approvals in recent years. Rules regarding compensating for the deaths of clinical trial research

subjects were released. India approved 19 clinical trials in the first four months of 2015, as compared

with 76 trials approved through the first five months of 2014, and 24 trials approved through the first

five months of 2013.

Benefits of the new submission system:

Creation of such an online system will help to protect the rights, safety and well-being of trial

subjects, as well as the authenticity of the data generated

The new online system will help in the collection and organization of information on sponsors,

contract research organizations, investigators, ethics committees and trial subjects.

Although online submissions are not mandatory currently however in the first phase of the launch of

the system, the online submission of applications of clinical trials can be made via the

website:http://octams.gov.in.

GVK Given clean chit by government panel in drug clinical trials

In December 2014, GVK was alleged for falsification in some of its BA/BE studies by French drug

regulator. Subsequently, the European Medicines Agency, after its preliminary investigations,

suspended sales and distribution of about 700 generic drugs across the EU.

The six-member multi-departmental expert panel, looking into GVK Biosciences alleged falsification

of drug trials data, inspected GVK Bio‘s facility and found no evidence of violations. The panel have

gone through data extensively and no data manipulation has been found. In fact, the one allegation

that has been made against the company was that the ECG data is falsified although when other

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regulators including FDA inspected GVK they did not found anything wrong. The panel, is yet to

finalize the report and submit to the government.

GVK was already given a clean chit by CDSCO (Central Drugs Standard Control Organization) and

findings were submitted to the expert panel.

The panel also pointed out that The French inspector did not give the basis on which he had

concluded the ECG data is falsified and therefore the panel has taken up the issue with the French

authorities, who are yet to respond.

MHRA begins to develop human factors guidance with stakeholders

The Medicines and Health products Regulatory Agency (MHRA) met with stakeholders to begin to

develop guidance on human factors to promote patient safety.

The Human Factors Task Group created by MHRA held its second meeting of 4 with external

stakeholders to begin to develop guidance on human factors for patient safety.

The group decided the guidance will be divided into 4 sections, which are:

regulatory framework/ pre-market (including settings/ end users)

regulatory framework/ post-market surveillance (including settings/ end users)

standards

simulation/ usablity

The guidance will be mainly aimed at the medical devices industry, although could be useful for

clinicians, procurement specialists and professionals with an interest in patient safety.

The group includes representatives from notified bodies, academia, NICE, trade bodies and

professional associations as well as representatives from the devices, licensing and vigilance and

risk management in medicines divisions at MHRA. Dr Brian Edwards of the Clinical Human Factors

Groupgave a stimulating presentation saying:

It‘s important to work together in particular areas where we have overlapping interests such as drug/

device combinations.

We plan to keep the group focused, inviting experts such as Brian Edwards to share their

knowledge.

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The group is chaired by Dr Peter Nightingale, who is also the chair of MHRADevices Expert Advisory

Group (DEAC). MHRA first held the group meeting on 27 February 2015, which was put together as

a result of a multi-disciplinary stakeholder day to engage on human factors and the implications for

patient safety. We plan to follow up on this work by sharing the draft guidance with a wider group of

stakeholders in Spring.

Source: https://www.gov.uk/government/news/mhra-begins-to-develop-human-factors-guidance-

with-stakeholders

AstraZeneca Pharma India to close Bengaluru API unit

Drug firm AstraZeneca Pharma India will close its Active Pharmaceutical Ingredient (API) unit

at Bengaluru due to low demand for the product in the export markets.

The Board of Directors of the company at its meeting held on December 2, 2015 has decided to

close the Active Pharmaceutical Ingredient (API) Unit at Yelahanka in Bengaluru, AstraZeneca

Pharma India said in a filing to BSE.

The company, however, did not disclose what it intended to do with the employees working at the

respective unit.

"The Board took the decision as Terbutaline Sulphate (TBS) was the last API to be manufactured at

the API unit and no other API manufacturing activity is planned to be carried out at this unit in the

future," it added.

The decision was taken following an application to the Drug Controller General of India(DCGI) to

withdraw the manufacturing licence for TBS, AstraZeneca Pharma India said.

The product was manufactured primarily for export and the company applied to withdraw the licence

following low demand in the export markets.

The company's tablet manufacturing plant that started commercial operations in 2013 will continue to

operate at the above mentioned location, AstraZeneca said.

Established in 1979, AstraZeneca India is present in seven areas of healthcare -

Cardiovascular, Diabetes, Oncology, Respiratory & Inflammation, Infection, Local Anesthesia and

Maternal Healthcare.

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Final report on national drugs survey likely to come by April 2016

Field data to the tune of 47,000 samples as part of national drugs survey which has been sent to 10

drug testing labs across the country is likely to release its final report by April 2016. Testing and

analysis on the same may conclude by December end this year, according to reliable sources.

Central Drug Testing Labs (CDTL) in Chandigarh, Mumbai, Hyderabad, Chennai, Kolkata and

Guwahati, state drugs testing labs at Gujarat, Karnataka Maharashtra and a lab at Indian

Pharmacopoeia Commission (IPC), Ghaziabad are part of testing and analysis.

According to an official, "The pan-India drugs survey will not do any partial testing but complete

testing for the first time in the history of India. The survey is significant as all studies till date have

been done only for spurious drugs and no 100 per cent testing for NSQ has been done till date. This

is for the first time that complete testing of NSQ drugs would be done as per Indian pharmacopoeia

and other pharmacopoeias." Only 10 per cent of the samples were tested during the pan-India study

done in 2009.

Collection of 47,000 samples was done successfully covering all the retail drug stores including

government medical stores, CHCs and PHCs as part of the pan-India survey. The exercise of pan-

India drugs survey is a mammoth exercise as it covers 29 states and 7 union territories. Around

1000 drug inspectors from across the country have done sampling of drugs from retail pharmacies,

CGHS dispensaries, ESI hospitals, Central Medical Stores Depots, PHCs and CHCs.

Following completion of sampling of spurious and not-of-standard quality (NSQ) drugs, the National

Institute of Biologicals (NIB) under the Union health ministry had sent samples to each of the seven

central drug testing labs across the country for testing to accomplish for the first time complete

testing of NSQ drugs. Only 10 per cent of the samples were tested during the pan-India study done

in 2009. This is for the first time that complete testing of NSQ drugs would be done as per Indian

pharmacopoeia and other pharmacopoeias.

For facilitating the process of analysis and testing through a specialised software the analysis of field

data on spurious and NSQ drugs is done online on a consistent basis. The survey, being done in

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collaboration with Indian Statistical Institute (ISI), Kolkata and Hyderabad and National Sample

Survey Organisation (NSSO), is a pan-India project in which drug samples were drawn from

healthcare institutions and retail pharmacies across the country to assess the quality of drugs

available to the patients.

In order to facilitate effective sampling of drugs by the drugs inspectors, all the 224 molecules

covering 15 therapeutic drug categories were assigned a unique sequence in the format developed

through a statistical design which ensures that the drug inspector can pick up samples only on the

basis of statistical design and not on their own.

Around 1000 drug inspectors and an equal number of NGOs were trained to execute the sampling

process to implement the study in the most meticulous and transparent manner. The analysis and

testing is facilitated through a specialised AKS software which helps in offering field data on spurious

and NSQ drugs online on a consistent basis in a seamless and flawless manner.

Earlier, a survey to assess the extent of spurious drugs in the country was conducted in the year

2009 by the ministry of health, which revealed that the extent of drugs found spurious was 0.046 per

cent only.

Sanofi, Shantha to supply polio vaccines for India's universal immunization scheme

India will join more than 110 countries that have introduced the injectable inactivated polio vaccine

(IPV) to their calendars. Sanofi and its Indian affiliate, Shantha Biotechnics, will supply polio

vaccines to the Indian government via UNICEF. The vaccines will be used in India's universal

immunization program.

Sanofi Pasteur has already supplied the government with its Imovax Polio vaccine, and Shantha will

soon follow suit with its ShanIPV. While oral polio vaccines have previously been included in the

nation's universal immunization program, the WHO recommends replacing it with the injected

inactivated vaccine, The Hindu Business Line reported.

While India is officially polio-free, it borders Pakistan and Afghanistan, which still report polio cases.

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"With the introduction of IPV in their immunization schedule, India moves the world much closer to

being polio-free," said Olivier Charmeil, president and CEO of Sanofi Pasteur, as quoted by The

Hindu Business Line. "As a company deeply rooted in India, we are very proud that vaccines

produced by both Sanofi Pasteur and Shantha will be used in this vital step towards a polio-free

world. We have worked as partners of the government of India for many years, with this day in

mind."

The goal is to eventually reach more than 20 million newborns annually through the program. The

rollout is gradual, with last month being the deadline to introduce IPV in 17 high-risk states and four

union territories,The Hindu Business Line reported. ShanIPV will be launched in 9 medium-risk

states in January and 6 low-risk states in March.

In February, a team of scientists in the U.K. won a $674 million grant from the Gates Foundation and

the WHO to develop an artificial polio vaccine. The existing oral polio vaccine uses a weakened

version of the poliovirus, which can cause infection in a few people, who can then spread the virus to

unvaccinated people. An artificial vaccine would not have this risk

Statistics and Process Validation: current Findings of the FDA

The "new" FDA's process validation guideline has been effective since January 2011. One

considerable change was made to the original validation guideline from 1987 to put a significantly

greater emphasis on statistics in the context of process validation. So far, relatively few inspection

deficiencies had been observed by the FDA with regard to statistics. At a conference in September

2015 co-sponsored by the FDA, Grace McNally - Senior FDA official - reported about current

"findings" in the 483s deficiency reports and in Establishment Inspection Reports (EIR). Now,

deficiencies regarding statistical problematics can also be found here.

For example, it has been criticised that a (statistical) sampling plan had be misinterpreted. Wrong

AQL values with regard to the number of samples have been noted based on MIL-STD-105D.

Moreover, it has been criticised that the company didn't know the operation characteristics of its

sampling plan.

Another criticised "finding" was that PPQ batches had been considered as "accepted" when all in-

process controls and release specifications were met. It has also been criticised that no intra-batch

variabilities have been examined. In addition, it has been noticed that there was no information

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available in the validation plan concerning the assessment of the process itself. There was also no

indication about the objective of the determination of inter-batch variabilities.

Although OOS results had been found in 2 out of 4 PPQ batches, reduced IPC tests have been

recommended in the PPQ report giving the justification that this was a standard procedure.

Regarding this point, the FDA criticises the lack of scientific rationales for reduced sampling and

monitoring. Interestingly, Grace McNally mentions possibilities for rationales of IPC sampling plans

and the adaptation to a reduced size. In this context, she refers to the ANSI/ASQ Z1.4 norm and ISO

2859 whereby it is expressly pointed out that the ANSI norm recommends the production of at least

10 successful batches before reducing testing. According to the ISO norm even 15 successful

batches are necessary.

The FDA notified a tablet process, criticising the fact that no rationales for warning and action limits

were available. Furthermore, it has been criticised that no analyses on variabilities were available

although they had been required internally and no capacity indices had been determined. There

have been no analyses on the distribution of data, neither planned nor performed. The FDA also

remarked that the calculation of variabilities is necessary to be able to make statements about

process capacities.

Conclusion: Reinforcing the emphasis on statistics in the US FDA Process Validation Guideline from

2011 hasn't been really often addressed in the official deficiencies reports. This seems to be

changing.

Identification of Medicinal Products Standards will apply in six Months

Over the last couple of years the European Health Authorities in conjunction with the International

Standards Organization (ISO) have been developing a set of global data standards referred to as

Identification of Medicinal Products (IDMP).

The Identification of Medicinal Products (IDMP) standards were developed in response to a

worldwide demand for internally harmonized specifications for medicinal products. The EU is the first

to implement these standards, and the other ICH regions will follow. The pharma sector must comply

with IDMP standards in the EU region starting July 2016. Following the EU, the other ICH

(International Conference on Harmonization of Technical Requirements for Registration of

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Pharmaceuticals for Human Use) countries will then begin their own adoption processes to ensure

global compliance.

Once the IDMP standards are implemented globally, detailed information about all medicinal

products worldwide will, for the first time, be available in a consistent format. This provides regulators

with the means of easily comparing product data across regions and with different manufacturers

and marketing authorisation holders. This increased transparency will drive numerous patient safety

initiatives. It also paves the way for the future roll-out of patient-centric initiatives such as 'e-

prescriptions'.

Adopting the IDMP standard should not only help to achieve regulatory compliance but wants also

improve internal business process efficiencies, as well as increase effectiveness between business

functions and with external partners, truly enabling a task to value strategy.

For additional information please visit the EMA IDMP Plaza page.

The QP Declaration: some Questions remain open

Marketing authorisations require a QP declaration (issued by the Qualified Person) to confirm that

the active substance (active pharmaceutical ingredient - API) has been manufactured in accordance

with the EU-GMP Guide, Part II: Basic Requirements for Active Substances used as Starting

Materials. This QP declaration is required from each registered EEA Manufacturer and Importer

Authorisation Holder (MIAH) that uses the API as a starting material and/or is responsible for QP

certification of the finished batch of a human or veterinary medicinal product.

The QP declaration template provides, in a format considered suitable for submission, a basis for

demonstrating compliance of the active substance manufacture with GMP requirements and that the

manufacturer has relevant knowledge of the supply chain.

However, more than one year after the final guidance was published, some questions remain open

or are frequently asked by the stakeholders. The Co-ordination Group for Mutual Recognition and

Decentralised Procedures - Human (CMDh) has now published an updated document in October

2015 to summarise the most frequent questions and answers.

Amongst others, the following questions are answered:

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Must the QP declaration consider only the final active substance manufacturer site and its

intermediate, or does it need to consider the manufacturing sites of the raw-materials used for

the first synthesis step?

When the only change in an updated CEP is the name of the HOLDER (the manufacturing

site remains the same) what is the rationale for requiring a new QP Declaration?

When a new API manufacturing site is added in an updated CEP, is it necessary to present a

QP Declaration for the already approved API manufacturers?

The answers and other Q&As can be found in the CMDh Q&As QP declaration document

CMDh/340/2015 (October 2015).

The European Medicines Agency's (EMA) original Qualified Person (QP) declaration template and

accompanying guidance, which intended to clarify the expecations, was already published in 2014.

Pharma companies „among happiest places to work‟

Five pharmaceutical companies have placed in a top 50 of the happiest companies in America

listing, based on reviews by employees, with two leading drugmakers making the top three.

Amgen, Novartis, Johnson & Johnson, MSD and Pfizer all ranked in online career community

CareerBliss‘ sixth annual 50 Happiest Companies in America awards list. The survey is compiled

using thousands of independent company reviews submitted to the CareerBliss site by employees

between 2014 and 2015.

The survey takes into account eight weighted factors relating to a happy working environment,

including: work-life balance, an employee‘s relationship with his or her boss and colleagues, the

office environment, job resources, compensation, opportunities for professional development, and

company culture.

Amgen and Novartis came second and third on the list respectively, while Johnson & Johnson

placed 14th. Also in the top 50 from the pharma industry were MSD, at 29th, and Pfizer at 33rd.

The number one ‗happiest‘ company according to the research was the health insurance provider

UnitedHealthcare, which offers an average employee salary of $67,856 – calculated from

CareerBliss‘ job listings from the company.

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Amgen and Novartis came second and third, respectively and both topped United for employee

salary. California-based Amgen offers average wages of $74,808, while third-placed Novartis pays

an average of $183,182.

Amgen climbed seven places from the 2014 listings and Novartis retained third place. Other

companies in the top 10 companies in all sectors were: Nokia, Total Quality Logistics, Texas

Instruments, Metropolitan Life Insurance Company, Chevron, Adobe Systems and Anthem – another

health insurer. Google meanwhile, fell 12 places from sixth to 18th, with an average wage of

$47,598. The list‘s highest climber was Paypal, which rose from 49th last year to 13th in 2015.

As well as salary, among employees‘ chief concerns in rating their companies were that they

received support to further and develop their careers, that they had positive relationships with

managers and that they felt part of a strong company culture.

Source: http://www.pharmafile.com/news/501704/pharma-companies-among-happiest-places-work

Seven-member committee to examine online drug sale issue

A seven-member committee has been formed to look into the the issue of online sale of drugs, Lok

Sabha was informed today.

Drugs Consultative Committee ( DCC) has constituted a seven-member sub committee to examine

the issue of online sale of drugs, while taking care of the risks and concerns related to such sales,

Minister of State for Chemicals and Fertilisers Hansraj Gangaram Ahir said in a written reply to Lok

Sabha.

"All measures considered necessary for safeguarding the interests of consumers are being taken by

the government", he added.

A number of representations have been received from chemists and druggist associations against

the online sale of prescription drugs, the minister said.

Similarly a number of representations have also been received to permit such sales, he added.

Replying to another question, Ahir said Ministry of Health and Family Welfare has constituted an

expert core committee to review and recommend the revision of National List of Essential Medicines

(NLEM) 2011 in the context of contemporary knowledge of use of therapeutic products.

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Indian Govt to introduce injectable contraceptives for women

Government has decided to introduce injectable contraceptives for women in the public health

system and family welfare programme, Union Health Minister J P Nadda said today.

"The government has decided to introduce injectable contraceptive for women in the public health

system and family welfare programme. In the first phase it would be launched only in the medical

colleges and district hospitals where dedicated counsellors for family planning are in place," the

minister said in reply to a question in Rajya Sabha.

He said that the government had conducted a high-level meeting of prominent gynecologists from

across the country including heads of departments of medical colleges and professional

and technical organisations which discussed the safety concerns in detail.

"It was concluded in the meeting thaptit menstrual irregularity and demineralisation of bones are

temporary phenomena which disappear once the injectables are discontinued. Rare case of

demineralisation of bones would be managed through external supplementation," Nadda said.

The first dose would be administered by a trained doctor in the facility after proper screening

and counselling and the government has planned dedicated technical content and capacity-building

plan for providers for all states, he said.

Google Life Sciences has a new name: Verily

Google Life Sciences got a rebrand today: It‘s now called Verily. A new site is up as well to illustrate

the company‘s emphasis on wielding technology ―to create a true picture of human health‖ – and

―effecting prevention.‖

Just as Google formed parent company ―Alphabet‖ earlier this year, it‘s clearly sticking to a literary

theme with ―verily,‖ which is a florid, Shakespearean way to say ―truth, truly, confidently.‖

Google Life Sciences was formed as an independent company, belonging to Alphabet, this past

August. Previously, GLS was simply the life sciences division of Google X. But as the

company sprawled and its emphasis on the life sciences continued to grow, its need for a life

sciences-focused division emerged.

Source: http://medcitynews.com/

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China toughens drug quality standards, rejects 13 applications

China's food and drug regulator said late on Monday it had rejected applications for 13 new drugs,

citing false or incomplete trial data, as the government toughens enforcement of quality standards.

The China Food and Drug Administration (CFDA) last month also rejected applications by eight

Chinese companies for inadequate trial data related to generic drugs for heart problems,

schizophrenia, pain, infections and other diseases.

The quality of locally made drugs is a priority for the government, which is pushing an ambitious

program of healthcare reforms to reduce reliance on both generic and more innovative imported

drugs.

The regulator's crackdown comes after it called on manufacturers to carry out their own internal

investigations into trial data in July, a move expected to raise the quality of local drugs over the long-

run, creating a challenge for global pharmaceutical firms.

The top 10 Chinese drugmakers have seen sales grow around 12 percent this year, according to

data from IMS Consulting, twice the rate of multinationals, which suffered a setback from a bribery

scandal at GlaxoSmithKline two years ago.

Source: http://www.reuters.com/

Texts adopted by the Ph. Eur. Commission

The European Pharmacopoeia Commission adopted 28 new monographs and 3 new general

chapters during its 153rd Session in Strasbourg from 17-18 November 2015.

The Texts will be published in the 9th Edition of the Ph. Eur. and shall become effective on 1st

January 2017.

As it has been previously published in Pharmeuropa 27.2 the commission adopted the deletion of

the test for Heavy Metals (2.4.8) from approx. 760 individual monographs on substances for

pharmaceutical use.

Among the new general chapters adopted is the general method Qualitative high performance thin-

layer chromatography of herbal drugs and herbal drug preparations (2.8.25).

The Commission also adopted 5 revised general chapters and 114 revised monographs, including

42 revised monographs on veterinary vaccines and the general monograph on Vaccines for

veterinary use (0062).

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The general monograph (0062) and three individual monographs (0447, 1939 & 2674) also include

promotion of the move from final product controls to consistency of production. What exactly is

meant by "consistency of production" will be subject of a dedicated press release to be published on

the EDQM website soon. There might be a correlation to the recently published Draft of Annex 17

(Draft Annex 17: Real Time Release Testing, Revision 1).

Additionally, drafts for revised chapters Substances for pharmaceutical use (2034)

and Pharmaceutical preparations (2619) in view of the ICH Q3D Guideline on Elemental impurities

will be published for public inquiry in Pharmeuropa 28.2.

For further Information please visit the EDQM Website.

GDP Interpretation: German Associations publish a Position Paper on Temperature

Deviations

In 2013, the revised EU Good Distribution Practice (GDP) Guideline was published in the Official

Journal. The extensive revision of the Guideline from 1994 has raised a lot of questions with regard

to the implementation. Some of the key concerns of stakeholders deal with temperature excursions

during transport.

Some expectations from the authority are particularly challenging. The associations of the medicinal

products manufacturers BAH, BPI, vfa and Pro Generika and the association of wholesalers

PHAGRO have now published a position paper and forwarded it to the regulatory authorities.

According to a report from the German Federal Association of Pharmaceutical Manufacturers (BAH)

very restrictive regulations - to some extent - concerning temperature-controlled transport have been

set by the authorities; particularly on hot days in summer where daytime temperatures exceed 25

degrees.

Beside the presentation of the associations' perception of the issue, the paper should also provide

arguments when assessing short-term temperature deviations during the transport of medicinal

products. The paper states that results from stability studies show that temperature fluctuations in

climate zone I/II (relevant zones in the European Union) do not necessarily lead to quality problems.

According to the paper, it can be concluded that it should be allowed to accept temporary

temperature excursions (except for refrigerated goods).

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In this context, the determination of the mean kinetic temperature (MKT) might be used to support

this. The MKT is defined as the kinetic average of all temperatures to which the medicinal product

has been exposed during storage and transport within the supply chain.

According to the arguments of the associations, the storage temperature indicated should always be

considered in connection with the full shelf-life. If a medicinal product is exposed to a temperature of

25°C for 36 months, this results in the same load as 33 months at 21°C and 3 months at 40°C.

Within the framework of the position paper, it is also referred to the Austrian Codex for the transport

of medicinal products in Austria last revised in 2014 (available in German language only). This

document has been released by the associations PHAGO and PHARMIG. The document states

(translated text - unofficial translation):

"Regarding the storage of medicinal products, a distinction is generally made between room-

temperature products and refrigerated ones. The storage rooms are accordingly qualified for these

temperature ranges. GDP requires that products are transported in an "acceptable range". This

formulation considers that for the distribution of medicinal products so many process steps (e.g.

loading, unloading, etc.) are executed. Given this fact- with regard to the use of economically

reasonable qualified standard transport systems - it is impossible to keep the storage temperature

defined at all times without interruption during the whole transport processes.

It is thus justified to define specific transport acceptance criteria on a risk-based approach for short-

term interruptions (up to 12 hours): "(…) By means of a risk analysis, it should be noted that the

influence of these short-term deviations (up to 12 hours) due to the transport on the stability and the

shelf-life is negligible with regard to maximum allowable degradation of the API over the entire

products life. (…)".

To what extent the GMP/GDP monitoring authorities will follow this interpretation will have to be

observed. The British Medicines Authority MHRA had published a Question & Answer document on

the use of the MKT values - please see our News on MHRA principles with regard to the possibilites

and the limits of the use of MKT.

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AstraZeneca commits £75m to replace warehouse and packaging unit at UK plant

AstraZeneca has invested £75m ($114m) to build packaging and warehouse facilities at its

manufacturing site in Macclesfield, UK.

According to AstraZeneca spokesman Andrew Higgins, the site in Macclesfield – about 20km south

of Manchester – is the largest pharma production facility in the UK and the second biggest in the

Anglo-Swedish firm‘s global network.

While the site has been subject to major job cuts in the past, Higgins told in-Pharmatechnologist.com

this investment is testament to AstraZeneca‘s commitment to the facility which - with the construction

of a new sterile manufacturing unit - puts the recent investment total close to £200m.

“We are constructing a new packaging unit, comprising of a hi-tech packing lines for tablets and

capsules, and an automated warehouse facility on the site, as the old one needs replacing,” he said.

Higgins added the project was complex and would take until 2019 as the firm is ensuring there will

be no disruptions to supply.

The project will create around 150 construction jobs, but once complete AstraZeneca's total

headcount will not increase, he added.

Zoladex

The site makes a number of products in AstraZeneca‘s small molecule portfolio, including the

blockbuster drug Zoladex (goserelin) delivered by a subcutaneous injection of a solid state deposit

that dissolves in the body over three months in patients with prostate cancer.

More systems training needed to help inspectors spot data falsification say PIC/S experts

Data falsification at API facilities is getting harder to spot say regulators who have called for

more systems training and international collaboration.

Regulators who attended the PIC/S Expert Circle on APIs in October said spotting faked or

manipulated records requires expert knowledge of increasingly complex systems.

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Attendee Carmelo Rosa, Director of the US FDA‘s Division International Drug Quality, told us

―inspectors need to feel comfortable with the systems used, and have an understanding of the things

a person can do in the electronic world in an attempt to hide, delete, substitute, or modify results.‖

He cited falsification of batch records and the practice of recording manufacturing activities before

they occur as common data integrity issues that inspectors encounter.

Rosa also suggested that because they know spotting such deficiencies takes time, some API

manufacturers even ―try to refocus the scope of the inspection, delay or deny access to critical

areas, which makes it difficult for the inspections.‖

To combat this some PIC/S members, including the US Food and Drug Administration (FDA), have

the power to say a drug is adulterated if an inspection is delayed, or if inspectors are denied access

to records or the site.

Delegates at the meeting, which was hosted by the European Directorate for the Quality of

Medicines & HealthCare (EDQM) in Strasbourg, France, also stressed the importance of regular

technical training for inspectors.

International collaboration

Collaboration was another major discussion point at the meeting, where national agencies were

urged to share more information with counterparts.

Rosa told us while regional regulators are working together and sharing information at an

―unprecedented level,‖ more needs to be done.

―More joint inspections are needed to continue harmonizing our inspection approaches and

outcomes‖ he said, adding that ―the more we interact, the more close we will get to relying on each

other’s inspection.”

Global

Membership of PIC/S provides a basic set of good manufacturing practices (GMP) guides for active

pharmaceutical (API) production and guides for the manufacture of sterile medicinal products.

The organisation also provides member organisations with seminars and training sessions relative to

APIs, computerized systems, human blood tissues, quality risk management and good distribution

practices.

PIC/S is also used by regulators to keep track of drugmakers‘ compliance with manufacturing

standards.

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The advantages of such collaboration were aslo stressed by MHLW director Haruo Akagawa at a

conference in Japan earlier this year.

He told delegates at CPhI Japan the membership of PIC/S - granted to the regulator and sister

organisation the Pharmaceuticals and Medical Devices Agency (PDMA) in July 2014 "the purpose

of PIC/S is to pursue and strengthen the cooperation established, to provide the framework for the

sharing of information and experience on a voluntary basis.

―I profoundly hope that [drug] candidates and innovative products will be delivered to patients as

soon as possible, not only from Japan but also for the whole world with assured international quality

levels and they will help patients suffering from diseases‖ he said.

FDA updates definitions: what constitutes a manufacturing site change?

The FDA is seeking comment on a draft guidance which outlines the administration‟s

thoughts on what constitutes a manufacturing site change.

The new guidance will replace an earlier document, ―Likelihood of Facilities Inspections When

Modifying Devices Subject to Premarket Approval,‖ which was issued August 5, 1999. However, this

guidance was never finalized. Today, based on industry feedback – and after gaining more than 15

years of experience – the FDA has made substantial revisions to the original guidance.

"Because the 1999 draft guidance was never finalized and in light of feedback the agency has

received over the last several years, the draft guidance on manufacturing site changes was issued to

solicit new comments that can be considered in an effort to finalize the document," an FDA

spokesperson told OutSourcing-Pharma.com.

The updated document outlines FDA recommended steps to help determine whether a PMA

supplement should be submitted in the event of a manufacturing site change (including a change to

the processing, packaging, or sterilization site).

Additionally, it discusses general factors the FDA may use to determine whether a preapproval

inspection is necessary before approval of the PMA supplement.

The document outlines several types of manufacturing site changes, including moving

manufacturing, processing, or packaging activities to a contract manufacturer not approved as part

of the original PMA.

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According to the FDA, ―This guidance should help manufacturers manage the timeframes associated

with implementing the changes in the manufacturing site and any processes, methods, procedures,

qualifications, and validations.‖

For a complete list of site change types, view Manufacturing Site Change Supplements: Content and

Submission .

The administration will be accepting comments until January 19, 2016.

Indian pharma market crosses Rs 1,00,000 crore mark: IMS Health

The Indian pharmaceutical market has for the first time crossed the Rs 100000 crore mark in

November when calculated on the basis of Moving Annual Total (MAT), said IMS Health, a global

pharmaceutical market research firm.

In its monthly review of the local market, IMS Health said in its note titled Market Reflections that

Indian companies took over three-fourth of the market share during the month.

On an average over the last three years, Indian pharmaceutical market has grown by 12%. Almost

38% of the market was dominated by drugs that treat infections, heart ailments and patients with

gastro-intestinal issues. IMS report said in November, Indian market was at Rs 100115 crore, of

which the retail sector was valued at Rs 84279 crore.

Sun Pharma remained at the top of the list of drug companies with a market share of 8%, followed

by Abbott with a share of 6.1%. Cipla trailed at 5.4% but grew higher than its top peers showing

growth of 16% during the month. Mankind Pharma has jumped past its traditional rivals to secure the

fourth position with a market share of 3.7%, standing above Alkem, GlaxoSmithKline and Zydus

Cadila.

Mixtard, a popular insulin marketed by Abbott, continued to hold the position of the largest brand for

the month followed by Pfizer cough syrup Corex and Glycomet-gp, a diabetes brand of USV.

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Sun says the FDA has issued warning letter for Halol plant

Since its key plant in Halol was written up by the FDA following an inspection last year, Sun

Pharmaceutical has gone all out to get on top of the agency's concerns. It has brought in outside

consultants and invested in new systems and employee training. But it wasn't enough to ward off an

FDA warning letter.

India's largest drugmaker acknowledged over the weekend that the FDA had formalized its concerns

with the plant in the warning letter. It said its effort to make changes began as soon as the FDA

inspection highlighted them in September 2014 and that it has communicated regularly with the

agency about its progress. But it says it will continue to work diligently until the FDA is satisfied.

"While our team is working hard to ensure that the commitments made to the U.S. FDA in

September 2014 are fully completed, we will continue to cooperate with the U.S. FDA and undertake

any additional steps necessary to ensure that the US Agency is completely satisfied with our

remediation of the Halol facility," Managing Director Dilip Shanghvi said in a statement.

Source: http://www.fiercepharmamanufacturing.com/

Novartis opens new office complex in Hyderabad

Novartis Group on Thursday opened its new office complex Novartis Knowledge City, the largest of

its five global service centres.

Telangana's Information Technology Minister K. Tarakarama Rao inaugurated the new complex of

Novartis Global Service Centers (NGSC), a nine-storied structure with a gross area of 800,000

square feet, or sufficient space to enable Novartis to absorb future growth.

The other global NGSCs are in Mexico City, Dublin, Prague, Kuala Lumpur.

With about 3,500 employees, Novartis Business Services (NBS) in Hyderabad provides services in

IT, financial reporting and accounting, human resources services, procurement and product lifecycle

services. Pharma development focuses on data management, statistics, regulatory affairs,

pharmacovigilence and clinical trial operations.

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Novartis, which started operations here in 2007, had two offices at Mindspace in the Hitec City,

which have now moved to the new complex, the company said in a statement.

The company's third location in the city - the lab facility at Genome Valley, will continue its operations

at the same site.

The company expects to drive collaboration, efficiency and productivity gains by providing

centralized services.

Source: www.business-standard.com

Novartis selling French Alcon plant to Recipharm

Novartis will shed another manufacturing unit as it continues its efforts to improve earnings by

getting more efficient. This time, it will sell an Alcon unit to Swedish contract

manufacturer Recipharm but has swung a deal to buy and continue to market the eye meds made

there.

Recipharm announced today that is buying Kaysersberg Pharmaceuticals, from Novartis' Alcon unit,

for €18 million ($19.7 million). With the deal, Recipharm gets a manufacturing plant in Kaysersberg,

France, with a line of products that it will supply to Novartis through a long-term manufacturing

agreement. It said the products will add about €36 million ($39.4 million) in sales for the company.

As part of the deal, which is set to close by year end, Recipharm will take on the 260 employees at

the plant but said the facility may "provide synergy with Recipharm's three other French facilities."

Recipharm said the Kaysersberg plant also has blow-fill-seal capabilities, adding a new niche for the

contractor.

"Blow-fill-seal technology is a very interesting area which we believe will grow and it therefore forms

an important addition to our portfolio," Recipharm CEO Thomas Eldered said in a statement.

The acquisition of Kaysersberg Pharmaceuticals continues a buying spree for the Swedish company

that has been picking up specialized assets around the world. It recently announced it was paying

about $105.2 million to buy a 74% stake in Nitin Lifesciences, an Indian sterile injectables CMO.

Source: http://www.fiercepharmamanufacturing.com/

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Granules India facility gets three observations during USFDA audit

Drug firm Granules India has received three observations from the USFDA for its Jeedimetla,

Hyderabad facility during a recent inspection.

US Food and Drug Administration (USFDA) completed the inspection of company's two facilities,

one located at Vizag in Andhra Pradesh and another at Jeedimetla in Telangana, Granules India

said in a regulatory filing.

"There are no observations for Vizag facility and three observations for Jeedimetla facility. The

company will respond to the observations in 15 business days", it added.

The Hyderabad-based firm serves customers in over 60 countries and has manufacturing footprint in

India and China.

It has three facilities in Hyderabad and one in Jingmen, China. A fifth factory is under construction in

Vizag through its JV company Granules OmniChem.

Source: http://economictimes.indiatimes.com/

TGA Half yearly performance report - January to June 2015

This half yearly performance report covers the period 1 January to 30 June 2015 inclusive.

Future reports will be published annually, with the next report covering July 2015 to June 2016. This

is in line with the report against the TGA key performance indicators and measures: Regulator

Performance Framework.

The KPI report outlines performance against our broad strategic intent, and should be read in

conjunction with the performance statistics provided in the future copies of this report.

Source: https://www.tga.gov.au/publication/half-yearly-performance-report-january-june-2015

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Honeywell Completes Acquisition Of Research Chemicals Business From Sigma-Aldrich

Honeywell today announced that it has completed the acquisition of the Seelze, Germany-based

laboratory research chemicals business from Sigma-Aldrich, broadening Honeywell's offerings for

high-purity solutions for drug discovery, medical diagnostic testing and other laboratory applications.

The acquisition includes the Fluka-branded solvents and inorganic chemistry portfolio worldwide and

the Sigma-Aldrich-branded solvents and inorganic chemistry portfolio in the European Economic

Area (EEA). Those offerings are now part of Honeywell's broader portfolio of offerings for research

chemicals, which already includes the Riedel-de Haën® and Burdick & Jackson® brands.

"The combined Honeywell business will be able to serve a broader range of customers and

applications with global brands recognized for world-class quality and lot-to-lot consistency –

essential for a range of applications including drug synthesis, food, environmental, chemical and

forensic testing," said Qamar Bhatia, president of Honeywell's Specialty Products business. "To

make the transition process as seamless as possible, customers will still order products directly

through Sigma-Aldrich and receive the same level of dedicated customer, technical and logistical

support as they always have."

The Honeywell portfolio now includes six product lines:

Fluka® chemicals and reagents used for biochemical research and other chemical and

pharmaceutical applications

Hydranal® Karl Fischer titration reagents used by laboratories to measure moisture content in

liquids and solids

Chromasolv® high-purity solvents for chromatography, a technique used to separate and

analyze complex mixtures

Riedel-de Haën® high-quality research chemicals used in pharmaceutical production and

bioscience

Burdick & Jackson® high-purity solvents, reagents and chromatography products for

laboratories and pharmaceutical production

Sigma-Aldrich® solvents and inorganics sold into the European Economic Area

PHARMA UPTODAY

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The acquired business employs approximately 200 people, primarily in Seelze, with sales and

marketing personnel throughout Europe. Honeywell's Seelze plant, which manufactures Riedel-de

Haën-branded products, currently makes the majority of the products in the acquired business.

The acquired business will be integrated into Honeywell's Fine Chemicals business and will continue

to be led by the core leadership team of the acquired company. With two production sites, Seelze

and Muskegon, Mich., in the U.S., the combined business unit will be able to develop and

manufacture high-purity research chemicals and other materials used in new drug discovery,

medical diagnostic testing and other laboratory applications.

With the addition of titration products, high-purity solvents and reagents, and specialty inorganic

chemicals, Honeywell builds on an already strong portfolio of Burdick & Jackson and Riedel-de Haën

products. Honeywell's Fine Chemicals business has supplied high-quality research chemicals and

specialty organic and inorganic compounds to the chemical and pharmaceutical industries for more

than 100 years. Its products are sold under the Burdick & Jackson and Riedel-de Haën brands, and

are used in a variety of laboratory, consumer and industrial applications including drug discovery,

toothpaste, water purification, fortified foodstuffs, polymer synthesis, and metal surface treatment

and finishing.

Honeywell Fine Chemicals is a part of the Honeywell Performance Materials and Technologies

business group.

Honeywell Performance Materials and Technologies (PMT) is a global leader in developing

advanced materials, process technologies and automation solutions. PMT's Advanced Materials

businesses manufacture a wide variety of high-performance products, including environmentally

friendlier refrigerants and materials used to manufacture end products such as bullet-resistant armor,

nylon, computer chips and pharmaceutical packaging. Process technologies developed by PMT's

UOP business (www.uop.com) form the foundation for most of the world's refiners, efficiently

producing gasoline, diesel, jet fuel, petrochemicals and renewable fuels. PMT's Process Solutions

business (www.honeywellprocess.com) is a pioneer in automation control, instrumentation and

services for the oil and gas, refining, pulp and paper, industrial power generation, chemicals and

petrochemicals, biofuels, life sciences, and metals, minerals and mining industries.

Honeywell (www.honeywell.com) is a Fortune 100 diversified technology and manufacturing leader,

serving customers worldwide with aerospace products and services; control technologies for

PHARMA UPTODAY

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buildings, homes, and industry; turbochargers; and performance materials. For more news and

information on Honeywell, please visitwww.honeywellnow.com.

This release contains certain statements that may be deemed "forward-looking statements" within

the meaning of Section 21E of the Securities Exchange Act of 1934. All statements, other than

statements of historical fact, that address activities, events or developments that we or our

management intends, expects, projects, believes or anticipates will or may occur in the future are

forward-looking statements. Such statements are based upon certain assumptions and assessments

made by our management in light of their experience and their perception of historical trends, current

economic and industry conditions, expected future developments and other factors they believe to

be appropriate. The forward-looking statements included in this release are also subject to a number

of material risks and uncertainties, including but not limited to economic, competitive, governmental,

and technological factors affecting our operations, markets, products, services and prices. Such

forward-looking statements are not guarantees of future performance, and actual results,

developments and business decisions may differ from those envisaged by such forward-looking

statements. We identify the principal risks and uncertainties that affect our performance in our Form

10-K and other filings with the Securities and Exchange Commission.

Source: http://www.laboratorynetwork.com/

AMRI Acquires Whitehouse Laboratories

AMRI today announced that it has acquired all the outstanding equity interests of Whitehouse

Laboratories, a leading provider of testing services that includes chemical and material analysis,

method development and validation and quality control verification services to the pharmaceutical,

medical device and personal care industries. Total consideration is $54 million in cash, and an

additional $2 million in shares of AMRI common stock contingent upon Whitehouse Labs achieving

certain 2015 targets.

"We are very pleased to acquire Whitehouse Labs, extending AMRI's analytical services expertise

and offerings, a critical function for all aspects of pharmaceutical development and manufacturing,"

said William S. Marth, AMRI's president and chief executive officer. "With the proliferation of ever-

tightening standards in the life sciences sector and mounting concern regarding quality and safety of

pharmaceutical products and medical devices, Whitehouse Labs meets the increasingly complex

PHARMA UPTODAY

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needs of customers we service and will augment our discovery, development and manufacturing

services nicely."

"For Whitehouse Labs, joining with AMRI validates our company's reputation and success and will

extend our ability to address customers' analytical and testing needs, which is a rapidly expanding

area of outsourcing within the life sciences industry," said Brian Mulhall, Co-Founder of Whitehouse

Labs. "Favorable dynamics are increasing the trend among biopharmaceutical manufacturers to

outsource testing services and our capabilities in analytical testing and diverse client base are highly

complementary to AMRI. We are very pleased to be joining the AMRI team and look forward to

working together to achieve our common goals."

Whitehouse Labs Background

Whitehouse Labs, based in Lebanon, New Jersey, operates a highly regarded analytical and testing

business with 2015 estimated revenue of approximately $11 million and 2015 estimated adjusted

EBITDA of approximately $6 million, implying a purchase price multiple of approximately 9 times

2015 adjusted EBITDA. Whitehouse Labs will continue to operate independently within AMRI's DDS

segment. Adjusted EBITDA excludes any deal related costs or purchase accounting impacts.

Whitehouse Labs offers a comprehensive array of testing solutions for life sciences from materials

and excipients, container qualification and container closure integrity testing, routine analytical

chemistry, drug delivery systems and device qualification programs, packaging, distribution, and

stability and storage programs.

About AMRI

Albany Molecular Research Inc. (AMRI) is a global contract research and manufacturing

organization that has been working with the Life Sciences industry to improve patient outcomes and

the quality of life for more than two decades. With locations in North America,Europe and Asia, our

key business segments include Discovery and Development Services (DDS), Active Pharmaceutical

Ingredients (API) and Drug Product Manufacturing. Our DDS segment provides comprehensive

services from hit identification to IND, including expertise with diverse chemistry, library design and

synthesis, in vitro biology and pharmacology, drug metabolism and pharmacokinetics, as well as

PHARMA UPTODAY

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natural products. API Manufacturing supports the chemical development and cGMP manufacture of

complex API, including potent, controlled substances, biologics, peptides, steroids and cytotoxic

compounds. Drug Product Manufacturing supports drug product development through commercial

scale production of complex liquid-filled and lyophilized parenteral formulations.

Cadila Healthcare slumps on receiving warning letter from USFDA

Shares of Cadila Healthcare have tanked 17% to Rs 320 on the National Stock Exchange (NSE) in

early morning trade after the pharmaceutical company received a warning letter from the US Food

and Drug Administration (USFDA) relating to its Moraiya formulation facility and Ahmedabad API

facility.

―The company has received a warning letter issued by the US FDA relating to its Moraiya formulation

facility and Ahmedabad API facility (Zyfine),‖ Cadila Healthcare said in a regulatory filing.

"The company said it will respond to US FDA to address the observations within the statutory time

permitted in the letter. The company is working hard to ensure that the commitments made to the US

FDA are fully completed. The company will continue to take all necessary steps to ensure that the

US FDA is fully satisfied with our remediation of the above facilities," it added.

Cadila has, however, clarified that there are no products in the US market which use API

of Zyfine facility.

―While it‘s too early to ascertain the impact on the numbers, as we also await more clarity on the

same. Also, the company has mentioned, that it will respond to USFDA to address the observations

within the statutory time permitted in the letter. Also, it‘s committed to resolve all the issues and

revamp our quality systems and processes and that there are no products in the US market which

use API of Zyfine facility,‖ says Sarabjit Kour Nangra, VP Research- Pharma, Angel Broking.

"On valuations front, the company is currently trading at 22xFY2017E earnings, thus leaving little for

comfort. In our assessment, after the correction, even in the best case scenario, the company has

upsides of only 7-8%", she adds.

During the 2QFY2016, the company had mentioned that, it has initiated site transfer of key filings

namely Asacol HD, Toprol XL and Prevacid OTD and expects it to be done over the next 6-9

months, the broking firm said in a client note.

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Cadila has already gained site transfer approvals for 4 of its existing products. Also, its new SEZ

formulations facility (oral Oncology, oral solids) received the Establishment Inspection Report (EIR)

from the USFDA. The company has undertaken 40+ filings over the past 3-4 years from this facility

paving the way for monetizing its large ANDA pipeline. Additionally the company is also hopeful of

commissioning its new sterile injectable facility located in Baroda by July 2016, added note.

At 12:56 p.m. the stock was down 15% at Rs 328 on the NSE. The trading volume on the counter

jumped multiple-fold with a combined 22.49 million shares representing 11% of total equity have

changed hands on the NSE and BSE so far.

Source: http://www.business-standard.com/

Terminology

A User Requirements Specifications (URS) document describes what the end

user needs a system to do. The document can prioritize the requirements as

mandatory, desirable, optional, or possible in future versions. Example: The

system must prevent false alarms due to normal activities such as door

opening.

A Functional Specification (FS) document describes the functions of a system

and how these functions satisfy the requirements in the URS. It also contains

the methods for verifying that these requirements have been met. It does

not define the inner workings of the system; rather, the FS describes

interactions between the system and its end users.

A Traceability Matrix (TM) is used to outline project requirements and

ensure they are met. Traceability matrices are usually in the form of a table

that is used to track requirements and/ or specifications that must be tested.

The matrix guides the development of testing documents, and should be

verified after tests are completed to ensure that all system requirements

have been adequately tested.

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New Guidance Australian regulatory guidelines for OTC medicines (ARGOM) (Nov 2015)

The Australian Regulatory Guidelines for over the counter medicines (ARGOM) assist applicants

and sponsors with the process of applying to either register new OTC medicine or make changes to

the registry details of a registered OTC.

The general changes include:

A landing page for OTC medicines guidance, which includes information on updates to guidance and

hyperlinks to all guidance material relevant to OTC medicines.

Presenting the guidance as accessible interlinking webpages with print options rather than the PDF

documents.

A step-by-step guide through the processes to register or make a change to a registered medicine

and the Advisory committee process.

Removing duplicated information to create webpages as a central source of information on specific

topics. For example the information about the regulation of OTC medicines and the expert Advisory

committee process that was duplicated in both the Guidelines on the pre-market application and

evaluation process for OTC medicines and Guidelines on change to OTC medicines have been

consolidated to create single webpages for:

o The overview of OTC medicine registration

o Expert Advisory committee process for OTC medicines which is accessed by hyperlink from Step 10

in the OTC new medicine registration process and Step 11 in the process to change a registered

OTC medicines.

New guidance identified by the word NEW on the OTC medicines landing page

Updated guidance is identified by the word UPDATED on the OTC medicines landing page

New content in guidance is identified by the word NEW on the relevant webpages enabling readers

to scan the webpage to readily identify any updated or new information

Source & more details: https://www.tga.gov.au/publication/australian-regulatory-guidelines-otc-

medicines-argom-nov-2015

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Guidance for Industry and Review Staff: Best Practices for Communication Between IND

Sponsors and FDA During Drug Development

The purpose of this guidance is to describe best practices and procedures for timely, transparent,

and effective communications between investigational new drug application (IND) sponsors and FDA

at critical junctures in drug development, which may facilitate earlier availability of safe and effective

drugs to the American public. This guidance describes:

• FDA‘s philosophy regarding timely interactive communication with IND sponsors as a core activity

• The scope of appropriate interactions between the review team and the sponsor

• The types of advice appropriate for sponsors to seek from FDA in pursuing their drug development

program

• General expectations for the timing of FDA response to IND sponsor inquiries

• Best practices and communication methods to facilitate interactions between the FDA review team

and the IND sponsor during drug development

• Expectations for appropriate methods, including the frequency, of such communications

Source: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance

s/UCM475586.pdf

FDA Guide for Microbial Vectors used for Gene Therapy

In October, FDA's Center for Biologics Evaluation and Research (CBER) published a draft guideline

dealing with the authority's recommendations concerning microbial vectors for the production of gene

therapy medicinal products. After its adoption, the new guide entitled "Recommendations for

Microbial Vectors used for Gene Therapy" will complement the current guide "Guidance for FDA

Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC)

Information for Human Gene Therapy Investigational New Drug Applications (INDs)".

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Nowadays, bacterial vectors such as Salmonella, Listeria or E. coli are genetically modified to

express therapeutically relevant compounds like tumour antigens, cytokines, growth factors,

therapeutic proteins, etc. for example, such vectors are generated by the modification of

chromosomal or episomal genes and the insertion of foreign genetic information. This may also lead

to modifications in the therapeutic profile or in the growth characteristics of the organisms.

Now with the new document, the FDA wants to give recommendations to the developing companies

and institutions, the investigational new drug application (IND) sponsors, about the information

needed with regard to the characteristics, production and control of such microorganisms (Microbial

Vectors used for Gene Therapy - MVGTs) for the submission of an IND. Moreover, the document

gives an overview of preclinical and clinical aspects.

The guide is composed of the following sections:

PRODUCT MANUFACTURING AND CHARACTERIZATION

Product Manufacturing – Components

Product Manufacturing – Procedures

Product Testing

Drug Substance

Drug Product

Stability Testing

Additional Testing

PRECLINICAL STUDIES

Animal Species and Models

Safety Evaluation

Attenuation Evaluation

Biodistribution/ Shedding

Antibiotic Use

CLINICAL STUDIES

General Considerations

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Prior Human Experience

Patient Population

Starting Dose, Dose Escalation, and Dosing Schedule

Treatment Modifications

Monitoring

For more details, refer complete guidance draft :

http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/

Guidances/CellularandGeneTherapy/UCM466625.pdf

EMA publishes Principles for QR Codes

The European Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh)

published a position paper in April 2014 on the use of QR codes on the outer packaging and the package

leaflet of nationally authorised medicinal products. Read more in the news CMDh Position Paper on QR

Codes published. QR stands here for "Quick Reponse".

Now, the European Medicines Agency (EMA) also released on 22 July 2015 details about the use of QR

codes on the outer packaging and package leaflet of centrally authorised medicinal products.

Following information can - for example - be made available via QR codes:

Package leaflet (completely or partially)

Excerpts from the SmPC

Training material (according to the risk management plan)

Diverse texts for which acceptance from the EMA is available

The regulations now adopted by the EMA comply with those for nationally authorised medicinal

products.

You can find EMA's tips on QR codes in the document Quick Response (QR) Codes in the Labelling

and Package Leaflet of centrally authorised Medicinal Products.

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A new general chapter on raw materials of biological origin will be published in the 9th

Edition of the European Pharmacopoeia

During the last European Pharmacopoeia Commission session held in Strasbourg on 17-18

November 2015, a new chapter was adopted for Raw materials of biological origin for the production

of cell-based and gene therapy medicinal products for human use (5.2.12). This general chapter is

published for information and includes sections on the risk, origin, production and quality

requirements of raw materials of biological origin used for the production of these advanced therapy

medicinal products. Read the Press Release Knowledge Database: information on substances and

methods of analysis, part of the work programme of the European Pharmacopoeia - See more at:

https://www.edqm.eu/en/node/14753#sthash.A2u5KOnZ.dpuf

Source: https://www.edqm.eu/en/node/14753

Draft Guidance on Pharmaceutical Quality/CMC: Draft Guidance for Industry on Advancement

of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base;

Draft Guidance for Industry; Availability

This guidance provides recommendations to pharmaceutical companies interested in participating in

a program involving the submission of chemistry, manufacturing, and controls (CMC) information

containing emerging manufacturing technology to FDA. The program is open to companies that

intend the technology to be included as part of an investigational new drug application (IND) or

original or supplemental new drug application (NDA), abbreviated new drug application (ANDA), or

biologic license application (BLA) reviewed by the Center for Drug Evaluation and Research

(CDER), and where that technology meets other criteria described in this guidance.

Source: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance

s/UCM478821.pdf

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Manual of Policies and Procedures (MAPP) FDA Pharmacy Student Experiential Program

This MAPP outlines CDER policies, procedures, and practices for CDER participating office and

division directors, administrative or management officers, preceptors, and

pharmacy students in the FDA Pharmacy Student Experiential Program (FDA PSEP).

Source: http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobac

co/CDER/ManualofPoliciesProcedures/UCM479186.pdf

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AUDIT FINDINGS - 483 Observations

Firm Name 483 Observation

West-Ward Pharmaceutical

Corp. - Feb. 26, 2014

Investigations of a failure of a batch or any of its components to

meet any of its specifications did not extend to other batches of

the same drug product.

Grandpa's Compounding

Pharmacy, Inc. - Sept. 18,

2015

Failure to reject any lot of components that did not meet the

appropriate written specifications for identity, strength, quality and

purity.

King Bio, Inc. - Sept. 4, 2015 The operations relating to the manufacture, processing and

packing of penicillin are not performed in facilities separate from

those used for other drug products for human use.

Cramer Products, Inc. - Oct.

26, 2015

The responsibilities and procedures applicable to the quality

control unit are not in writing.

Naturich Labs, Inc. - Aug. 26,

2015

The responsibilities and procedures applicable to the quality

control unit are not fully followed.

Johnson & Johnson

Healthcare Products, Division

of McNeil PPC, Inc. - Sept. 21,

2015

Investigations of a failure of a batch or any of its components to

meet any of its specifications did not extend to other batches of

the same drug product and other drug products that may have

been associated with the specific failure or discrepancy.

RC Compounding Services, LLC - Sept. 14, 2015

Procedures designed to prevent microbiological contamination of

drug products purporting to be sterile do not include validation of

the sterilization process.

Kutol Products Co. - Sept. 29, 2015

There are no written procedures for production and process

controls designed to assure that the drug products have the

identity, strength, quality, and purity they purport or are

represented to possess.

Pi Pharma, Inc. - Sept. 11, 2015

You did not establish product specifications for the purity, strength,

and composition of the finished dietary supplement.

Progela, S.A. de C.V. - Aug. 5, 2015

Raw or source data not generated for identification test.

Petnet Solutions,Inc. - Oct. 15, 2015

Laboratory records did not contain a complete record of all data

obtained in the course of each test.

Nephron Pharmaceuticals Corp. - Aug. 14, 2015

Drug products failing to meet established standards,

specifications, and quality control criteria are not rejected.

Cape Apothecary, Inc. - Oct. 7, 2015

Procedures designed to prevent microbiological contamination of

drug products purporting to be sterile are not established.

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Alex C. Fergusson, LLC - Sept. 11, 2015

Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the identity and strength of each active ingredient prior to release.

Deva Holding AS - Cerkezkoy Subesi - Aug. 6, 2015

Deviations from written specifications, test procedures, and laboratory mechanisms are not recorded and justified.

Intas Pharmaceuticals, Ltd. - July 3, 2015

The quality control unit lacks authority to review production records to assure that no errors have occurred and fully investigate errors that have occurred.

Bajaj Medical, LLC - Oct. 16, 2015

The written stability testing program is not followed.

Amneal Pharmaceuticals, LLC - Oct. 16, 2015

Investigations of a failure of a batch or any of its components to meet any of its specifications did not extend to other batches of the same drug product.

CSL Behring Pty, Ltd. - Oct. 9, 2015

Performance Qualification studies reviewed for the ... Filling Facility autoclave and … are inadequate.

Sovereign Pharmaceuticals, LLC - Aug. 21, 2015

Protective apparel is not worn as necessary to protect drug products from contamination.

Digestive Care, Inc. - Sept. 25, 2015

Deviations from production time limits are not justified and compromise the quality of the drug product.

FDA Warning letters

US FDA Warning letter: Sun Pharmaceutical Industries Ltd., Halol Plant, Gujarat, India:

1. Your firm failed to establish and follow appropriate written procedures that are designed to

prevent microbiological contamination of drug products purporting to be sterile, and that include

validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

You failed to perform adequate unidirectional airflow studies (smoke studies) under dynamic

conditions to determine how the movement of air and personnel during aseptic operations

could pose risks to product sterility.

Your aseptic processing equipment is not properly designed

You rejected vials during media fills without written justification or explanation.

Your media fill reconciliation records failed to include a specific description of the reason why

your firm rejected vials from each batch

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2. Your firm failed to maintain floors, walls, and ceilings of smooth, hard surfaces that are easily

cleanable in aseptic processing areas (21 C.F.R. 211.42(c)(10)(iv) and (i).

The floors, walls, and ceilings in your aseptic processing area were not maintained as

smooth, hard surfaces that were easily cleaned.

3. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch

or any of its components to meet any of its specifications whether or not the batch has already been

distributed (21 CFR 211.192).

You attributed the failures to product degradation from your process, but you failed to identify

the specific impurities or their root causes.

You also failed to notify the FDA of these stability failures

Unknown peaks were not thoroughly investigated

You failed to initiate an investigation for an extraneous peak identified during the analysis

of residue in your cleaning validation report

You did not initiate an investigation to determine the root cause for this extraneous peak at

the time of the event.

4. Your firm failed to establish and document the accuracy, sensitivity, specificity and

reproducibility of test methods employed by the firm (21 C.F.R. 211.165(e)).

You did not evaluate the accuracy of your dissolution test method

Method validation failed to evaluate the capacity to separate unknown late-eluting peaks

Sterile gloves intended for use in the manufacture of sterile products were partially immersed

in (b)(4) medium. The investigator found that the fingers of the gloves were not immersed and

the test method was not validated

5. Your firm failed to routinely calibrate, inspect, or check according to a written program designed

to assure proper performance and to maintain adequate written records of calibration checks and

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inspections of automatic, mechanical, or electronic equipment, including computers, used in the

manufacture, processing, packing, and holding of a drug product (21 C.F.R 211.68(a)).

You have been using an un-validated and unqualified Agilent data acquisition unit (DAU) to

monitor the temperature of the microbiological incubation rooms for media filled vials.

6. Your firm failed to establish appropriate controls over computers and related systems to assure

that changes in master production and control records or other records are instituted only by

authorized personnel (21 CFR 211. 68(b)).

You lacked audit trails or other sufficient controls to facilitate traceability of the individuals who

access each of the programmable logic controller (PLC) levels or Man-Machine Interface

(MMI) equipment.

For complete details

browse: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm478393.htm

US FDA Warning letter - One Way Drug, LLC 7/22/15 (WL: 441276), Las Vegas, NV:

FDA investigators also noted CGMP violations at your facility, causing the drug products for which

you have not obtained valid prescriptions for individually-identified patients to be adulterated under

section 501(a)(2)(B) of the FDCA. The violations include, for example:

1. Your firm failed to establish and follow appropriate written procedures that are designed to

prevent microbiological contamination of drug products purporting to be sterile, and that include

validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

2. Your firm failed to establish an adequate system for monitoring environmental conditions in

aseptic processing areas (21 CFR 211.42(c)(10)(iv)).

3. Your firm failed to establish an adequate system for cleaning and disinfecting the room and

equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).

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4. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug

product from contamination (21 CFR 211.28(a)).

5. Your firm failed to adequately design the facility with adequate separation or defined areas or

such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(b)).

6. Your firm failed to clean and, where indicated by the nature of the drug, sterilize and process

containers and closures to remove pyrogenic properties to assure they are suitable for their intended

use (21 CFR 211.94(c)).

7. Your firm does not have, for each batch of drug product purporting to be sterile and/or pyrogen-

free, appropriate laboratory determination of satisfactory conformance to final specifications for the

drug product (21 CFR 211.167(a)).

8. Your firm failed to establish and follow an adequate written testing program designed to assess

the stability characteristics of drug products and to use results of such stability testing to determine

appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

For complete details

browse: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm474639.htm

US FDA Warning letter - Thomas S. Tooma, M.D. 11/2/15 (clinical site), California:

1. You failed to submit an IND for the conduct of a clinical investigation with an investigational new

drug that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a), (b) and 312.40(a), (b)].

2. You failed to ensure proper monitoring of the clinical investigations [21 CFR 312.50 and

312.56(a)].

3. You failed to maintain adequate records of the disposition of the drug, including dates, quantity,

and use by subjects [21 CFR 312.62(a)].

For complete details

browse: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm474234.htm

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EU Non Compliance Report

EU Non-Compliance Report: Iason Italia SRL, Italy

Nature of non-compliance :

During the inspection 19 deficiencies were identified, 3 of them were rated as critical deficiencies

and 11 as major deficiencies.

The main deficiencies were related to the Quality Management and the Quality Assurance Systems

also in terms of sterility assurance and risk of contamination/defects of the final product.

One critical deficiency was related to failure to fully investigate and document out-of-

specification results for microbiological environmental monitoring in class A isolator

and class B/C surrounding areas, in manufacture of radiopharmaceuticals aseptically

prepared.

The company didn‘t carry out an appropriate and full-scale investigation to determine

what caused the OOSs.

An appropriate level of corrective action analysis was not applied during the

investigation and the true root cause(s) were not determined.

Failure to address the root cause due to ineffective CAPA revealed a lack of the

quality assurance framework system.

Another critical deficiency was reported with regards to production processes which

were considered not satisfactory controlled: it was found that for the manufacture of

some batches of the radiopharmaceutical Pcolina (Iasocholine) a non suitable reagent

was used (expired dibromomethane).

Moreover, for some batches of released RPs master batch documents were

incomplete.

No adequate review by QA or QP.

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Furthermore, preparation of the starting material set for radiopharmaceuticals was

performed in condition not appropriate to guarantee an adequate level of chemical

and microbiological containment.

The inspection‘s team has rated also as critical the observation related to the number

of personnel in force to the manufacturing site, which were considered not appropriate

to conduct all the activities in accordance with the GMP and to maintain the quality

management system and its effectiveness.

The remaining major deficiencies were related to specific aspects of the Quality

Assurance System with regards to PQR assessment, revalidation and recalibration of

critical equipment, data integrity in the context of HPLC management, storage of

materials and documentation system.

EU Non-Compliance Report: AstraZeneca Pharma India Ltd., India

Nature of non-compliance :

The API manufacturing process was not acceptably validated and was not under control after the

validation.

The concerned batches have been sent to the EEA (Sweden) and to a third country (China). During

the inspection, 24 deficiencies were found. None of the deficiencies was critical but 4 were major.

The 4 major deficiencies were found in the areas of documentation routines and data integrity (2),

design and maintenance (1), validation (1). After three CAPA responses from the company the major

deficiency regarding validation still remains.

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Investigations:

Unexpected results and/or events should be

documented and thoroughly investigated.

It is not sufficient to determine that additional training

is required for the analyst or glassware wasn’t

adequately cleaned.

Regardless of the method used, the investigation steps

and results need to be clearly documents.

Include supporting documentation so that anyone

reading the investigation report understands the

actions taken and the corresponding results.

In the event that the cause cannot be identified, be sure

the investigation report illustrates that adequate

measures were taken to attempt to identify the cause.

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Regulations of the Month

Subpart C--Buildings and Facilities

Sec. 211.48 Plumbing.

(b) Drains shall be of adequate size and, where connected directly to a sewer, shall be

provided with an air break or other mechanical device to prevent back-siphonage.

Sec. 211.50 Sewage and refuse.

Sewage, trash, and other refuse in and from the building and immediate premises shall be

disposed of in a safe and sanitary manner.

Sec. 211.52 Washing and toilet facilities.

Adequate washing facilities shall be provided, including hot and cold water, soap or detergent,

air driers or single-service towels, and clean toilet facilities easily accesible to working areas.

Sec. 211.56 Sanitation.

(a) Any building used in the manufacture, processing, packing, or holding of a drug product

shall be maintained in a clean and sanitary condition, Any such building shall be free of

infestation by rodents, birds, insects, and other vermin (other than laboratory animals). Trash

and organic waste matter shall be held and disposed of in a timely and sanitary manner.

PHARMA UPTODAY

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Top Presentations of Pharma Uptoday

· Presentation on data integrity in Pharmaceutical Industry

· Data Integrity II - Chromatography data system (CDS) in Pharma

· Good chromatographic practices

· HPLC - Peak integration for chromatography

· Good Laboratory Practices for Pharmaceutical Quality Control Laboratories

· Laboratory Errors

· Understand the importance of each step to minimise Laboratory errors

· Sample preparation techniques of solid dosage forms

· Investigating aberrant potency values in Pharma Analysis

· All about Tablets (Pharma)

The module Consult Yourself.... “Know Regulation - No Observation” deals with most common

(top 20) basic CFR regulations having frequent violations and previous observations for better

understanding.

#1 "21 CFR 211.160" http://www.slideshare.net/skvemula/top-20-observation-series-1-21-cfr-211160

(Subpart I--Laboratory Controls: Sec. 211.160 General requirements.)

#2 "21 CFR 211.22" http://www.slideshare.net/skvemula/top-20-observation-series-2-21-cfr-21122

(Subpart B--Organization and Personnel: Sec. 211.22 Responsibilities of quality control unit)

#3 "21 CFR 211.192" http://www.slideshare.net/skvemula/top-20-observation-series-3-21-cfr-211192

(Subpart J--Records and Reports: Sec. 211.192 Production record review.)

#4 "21 CFR 211.67" http://www.slideshare.net/skvemula/top-20-observation-series-4-21-cfr-21167

(Subpart D—Equipment: Sec. 211.67 Equipment cleaning and maintenance)

#5 "21 CFR 211.100" http://www.slideshare.net/skvemula/top-20-observation-series-5-21-cfr-211100

(Subpart F- Production and Process Controls: Sec. 211.100 Written procedures; deviations.)

PHARMA UPTODAY

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#6 "21 CFR 211.165" http://www.slideshare.net/skvemula/top-20-observation-series-6-21-cfr-211165

(Subpart I--Laboratory Controls: Sec. 211.165 Testing and release for distribution)

#7 "21 CFR 211.42" http://www.slideshare.net/skvemula/top-20-observation-series-7-21-cfr-21142-

subpart-cbuildings-and-facilities-design-and-construction-features

(Subpart C-Buildings and Facilities – Design and construction features)

Few Pharma Uptoday topics can be accessed from our website

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