Analytical Instrument Qualification that Meets USP, EP and JP Guidelines

Author: Paul A Coombes

Analytical Instrument Qualification (AIQ) is a requirement for pharmaceutical companies, this is clear. The real issue is how to devise an AIQ program that is compliant and cost-effective.

The United States Pharmacopeia (USP), European Pharmacopeia (EP) and Japanese Pharmacopeia (JP) provide a mixed picture of guidelines and rules on this topic. USP has a general chapter on AIQ and now increasingly includes new chapters with some AIQ specifications. The EP includes specifications that UV and IR spectrophotometers must meet to be used for EP materials testing. JP has similar sections to EP but sometimes adds an extra test and specification.

In all cases the concepts and prescribed specifications are for all instruments within a technique and, of course, not biased to different makes and models of instrument. Therefore it makes sense for laboratories to use ‘universal’ qualification test protocols for each technique, not specific to makes and models or manufacturers’ brochure specifications, but designed to prove compliance (where applicable) to the USP, EP and JP within the intended range of use and in the users’ environment.

• Regulatory specifications and standards as found in the pharmacopeia take precedence.

• In the absence of pharmacopeial specifications refer to regulatory guidance literature, expert literature and your own company policies, procedures and SOPs.

• The intended use of your instruments – not the manufacturers' brochure specifications – guides the AIQ protocol for type of tests, set points of the tests and the acceptance limits.

• Remember to include compliance to over-arching regulations such as 21 CFR Part 11 and Annex 11 concerning electronic records; good documentation practices, health and safety limitations and general good science and lab working practices.

Definition of: • DQ / IQ / OQ / PQ • Roles & Responsibilities

Risk Management: • Grouping of Instruments A / B / C…. • Reduced requirements for Group A saves time & money for

industry

AIQ - Major Areas Analytical Instrument Qualification

AIQ is the foundation of data quality

Simplification of the Process: • Straightforward • Easy to understand • Harmonization

OQ

Compliance to Pharmacopeia is the critical criteria here It does not matter what make or model; new or old; high-spec or economy low spec UV-Vis

Spectrophotometer you have – if it is used for analysing materials to EP the instrument must meet the EP specifications.

Again this implies a single OQ protocol for all makes and models.

But what about the other two major pharmacopeia USP and JP?

Until today, only the JP had more to say about UV-Vis Spectrophotometer specifications than EP. The JP has requirements for repeatability of measurement that must be included in the OQ tests of

any globally compliant protocol.

The USP for years never had any specific instrument specifications for UV-Vis or Infra-Red Spectrophotometers – so it was never really appropriate to claim your OQ protocol for UV-Vis or IR instruments was compliant to USP because there were no specifications with which to be compliant

- until now!

USP Chapter <857> ULTRAVIOLET-VISIBLE SPECTROSCOPY

USP Chapter <857> is in process and soon to be relevant to this topic. New chapters like this are in the pipeline and will have a similar structure of sections: Introduction Qualification Installation Qualification Operational Qualification Performance Qualification Validation and Verification The creators of compliant OQs for UV-Vis instruments now must analyse and interpret the three main inputs and create a test design that covers all three in the most efficient manner…

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Abstract

The Primary Inputs to Designing AIQ protocols

Definition of Terms – Why not use USP <1058> definitions?

Simple Implications of Following USP …

Instrument Specifications in EP for UV-Vis … How to be compliant to pharmacopeia and meet the needs of user range and user limits?

Throughout the previous three decades the use of different terms and words, and different definitions of the same words, has confused newcomers and auditors and slowed down expert practitioners’ progress in this field. The definitions in USP Chapter <1058> are acceptable, authoritative and suitable for any global approach to the subject. Therefore, PerkinElmer OneSource Laboratory Services decided to re-write its Qualification Documents Policy to incorporate these and only these definitions and to offer AIQ services with protocols that match these definitions.

Key definitions for this poster – all from USP <1058> [except text in italics] The term Validation is used for manufacturing processes, analytical procedures and software procedures and the term Qualification is used for instruments. Operational Qualification (OQ) is the documented collection of activities necessary to demonstrate that an instrument will function according to its operational specification. OQ tests are specifically designed to verify the instrument’s operation according to specifications in the user’s environment. Performance Qualification (PQ) is the documented collection of activities necessary to demonstrate that an instrument consistently performs according to the specifications defined by the user, and is appropriate for the intended use. [Consensus use of the term PQ is now for customer performed routine tests (often same as or called system suitability tests)].

Firstly, use all the right words and terms in the documents!

For laboratory instruments the term is

Qualification – not validation or verification etc.

…and the annual qualification by vendors is OQ – not OQ/PQ, IPV, PV, PM etc.

OQ tests are specifically designed to verify the instrument’s operation according to specifications in the user’s environment.

It follows that if your lab had multiple makes of HPLC all performing the same set of analytical methods - then a single annual OQ protocol containing all the same

OQ tests and limits that reflect your use range should be followed.

Using each manufacturers’ different default OQ protocol is highly unlikely to meet this requirement. And is confusing & time-wasting for auditors…

The state-of-the-art OQ protocol would allow for custom configuration of all set points and limits to meet specific user requirements, while providing fixed default limits at the pharmacopeia or industry standards.

How to be compliant to good science, good document practice and Part 11?

• The PerkinElmer UOQ has paper records and .xps ‘digital paper copies’.

• Approved copy of the Review Protocol PDF can be locked and saved.

• Paper report folder is the primary original record, which is provided to the customer for ink signatures and storage on-site.

• Electronic copy of OQ Final certificate (XPS file) is completely secure.

ELECTRONIC FILES

THAT ARE SEARCHABLE,

SHAREABLE, AND SECURE

HPLC Pump Flow testing uses a highly accurate calibrated digital flow meter data logger that sends completely secure time-stamped data file directly into the OQ report for PASS/FAIL reporting against the default limits and any custom-configured limits.

The most reliable LC pump testing available.

Summary The poster shows examples of the thought process and practical implementation that goes into making high quality, efficient instrument compliance protocols and services. Using a single qualification protocol and consistent modern data handling for all your GMP/GLP instruments (within a technique such as LC, GC, UV, IR etc.) meets the concept held by authors of pharmacopeia and regulatory agencies such as U.S. FDA because they are concerned with seeing trustworthy evidence that your instruments meet relevant performance requirements regardless of their age, cost, make or model. This approach has the added advantage of allowing true comparisons of different makes and models in all your laboratories locally or around the world. This universal format data significantly aids method transfer and technology transfer strategies and provides business analytics data. PerkinElmer OneSource customers around the world already benefit from our Universal Operational Qualification (UOQ) services that are designed to meet all the above concepts.