Project Management of Chemical, Analytical, and Formulation Development

Project Management of Chemical, Analytical, and Formulation Development

-Vishnu Datta M

Project Management of Chemical, Analytical, and Formulation Development

Project Management of Chemical, Analytical, and Formulation Development

• Introduction• Chemical Development• Formulation Development• Analytical Development• Primary and secondary

Manufacturing• CMC Project –management

strategies

Introduction

• Project-managing the closely related development disciplines of chemical, analytical and formulation development.

• The relationship of these activities both within the chemistry manufacturing and controls and with other project team activities is described from project planning perspective

IntroductionIntroduction

• Key CMC activities supporting the registration submission are performed to a demand system of quality control known as GMP this requires sponsors to be able to provide evidence that the manufacture of drug product has been compliant to GMP requirements.

• A number of important challenges emerges from the above that set the framework for the phases of CMC development for a new chemical entity entering pre-clinical development

Chemical development

• Chemical development group is tasked with discovering a robust and viable commercial process for the synthesis of drug substance on a manufacturing scale and to transfer this technology to the site of manufacture.

• With the focus now on a selected development molecule route optimization can proceed

Chemical developmentChemical development

• There are three main phases to the work carries out in chemical development

• The rapid establishment of a viable supply route to fund activities of other development groups.

• Discovery of the best synthetic sequence i.e. identifying the key intermediates

• Development of the best synthetic sequence into a safe economic primary manufacturing process

• To achieve this objectives a through understanding of the chemistry involved in the each step of the synthesis is required

Supply route

• The first task is to establish a viable route of supply capable of preparing the required quantities of drug substance for early development needs.

• Modifications to the med-chem route would be quickly established in the laboratory and in some cases a completely new approach would be adopted prior to the scale up in the laboratory or pilot plant

Best routeBest route

• >>>this stage of work carries out by chemist in chemical development requires retero-synthetic analysis and the use of chemical literature online data basis to propose several paper chemistry route to the desired drug substance

• The routes are prioritized and evaluated in the laboratory and the most appropriate sequence is chosen and scaled up further in the lab and pilot plant

Final manufacturing process

• In this stage of the work carried out by the chemist in chemical development the best reagents solvents and conditions need to be established for each transformation in the final synthetic sequence.

Formulation DevelopmentFormulation Development

• Formulation development programme will be tailored according to the type of pharmaceutical form to be marketed.

• To illustrate the type of activities that commonly have to be undertaken in formulation development the text will focus on chronic therapy.

Formulation Development

• The drug will likely need to be formulated to enable it to be adequately orally absorbed in animals and in humans

• Animal toxicology studies will often require a formulation of the drug that can be administered by oral gavage in some studies capsule formulation can be used in larger animalssuch as dogs

Formulation DevelopmentFormulation Development

• The clinical trials are performed according to the regulations of the respective country

• To restore the drug for market data have to be submitted to regulatory agencies to support the shelf life of the product as it is prescribed in the package insert an adequateshelf life is important for a chronic therapy drug.

Formulation Development

• The formulation group will structure their work programme to meet the demands

• Physico-chemical characterization of drug is usually conducted in selection of the lead

• Pre formulation studies are performed• Dissolution drug testing will define

whether the drug sufficiently rapidly released

Formulation DevelopmentFormulation Development

• Since the optimum clinical dose is not known several strengths of dose may be made

• The results from these studies will influence the packaging that will be used

Analytical DevelopmentAnalytical Development

• This supplies to the process of manufacture of the drug substance and to the formulated drug product

• The measurement of purity of drug substance and the impurities and the degradants will require the establishment of validated assays and synthesis of reference standard.

Primary and secondary manufacturingPrimary and secondary manufacturing

• Primary manufacturing refers to achieve pharmaceutical ingredients manufacture and secondary manufacturing to the drug product manufacture.

• The drug product consists of the formulated tablet with distintive shape color marking together wit hthe primary packaging which may be blister pack secondary packaging which may be a carton with labeling that will have to meet the regulatory requirements

CMC project management strategies

• The main challenges the CMC team faces can be broadly summarized as follows:

To reduce the timeTo reduce the riskTo reduce the cost

strategies

•Sourcing the work In-house and/or at contract•Central laboratories•Cost management and tendering process•Regulatory affairs

•Reducing time to market•Expert consultants

•Running the CMC team

CMC team

~~REFERENCES~~~~REFERENCES~~

• Pharmaceutical Regulatory Management-2nd edition vol.182edited by Tony kennedyInforma health care

~~Thank you~~~~Thank you~~

• The key is to keep company only with people who uplift you, whose presence calls forth your best.

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