March Harmonization of Standards for Better Regulatory Compliance

Transcription

1 March 2010 Harmonization of Standards for Better Regulatory Compliance

2 Contents Abstract 2 High Level Interpretation of USP<1058> 3 High Level Interpretation of ASTM E Aligning ASTM E2500 concepts to USP s AIQ Process 5 Conclusion 6 References 6 Why HCL? 7 About the Author 7 ABOUT HCL 8 Abstract Keeping abreast of the recent developments in the harmonization of standards is essential for better Regulatory Compliance. This white paper offers an opportunity for the Scientists or Analysts who are working in the Laboratories of Pharmaceutical industry to gain an interesting understanding of a harmonized framework as it relates to the Analytical Instrument Process. Analytical Instruments are being used in the laboratories of Pharmaceutical industries for testing various kinds of samples. The samples could be either from Research and Development or from Manufacturing activity. The Quality and Integrity of the Analytical Data is very important as they are playing a vital role in taking quality related decisions. Moreover, the Scientific Supporting Data generated by these Analytical Instruments are being used for the Regulatory Submissions. So the regulatory importance of ensuring the validated state for the Analytical Instruments through appropriate process is very high. It is mandatory to perform Analytical Instrument before deploying into regular laboratory use. This white paper provides a high level interpretation of both USP <1058> and ASTM E2500. It also depicts better regulatory compliance by applying some of the concepts of ASTM E2500 to the Analytical Instrument process as detailed in United States Pharmacopoeia s General Chapter 1058.

3 High Level Interpretation of USP<1058> The United States Pharmacopeia National Formulary (USP-NF) is a combination of two official compendia of public pharmacopeial standards. USP<1058> denotes General Chapter 1058 within United States Pharmacopeia (USP) which addresses the details of Analytical Instrument (AIQ) process. Analytical Instrument is the process of obtaining documentary evidence and determining that the instrument functions suitable as intended. USP divides the AIQ process into four phases. Design (DQ), Installation (IQ), Operational (OQ) and Performance (PQ). Analytical Instrument Process Vendor s Site Structurally Validated Products DQ Before Purchase Owner s Site Functional Validation Installation Operational Performance IQ OQ PQ Before use System Suitability During Use Owner s Site Maintenance Module Accuracy Calibration Owner Performed PQ After use Figure 1 Figure 1 represents the high level Analytical Instrument Process. The final responsibility of Instrument lies with the Users. The Quality personnel ensure compliance requirements during the AIQ process. The manufacturers are responsible for the DQ and the validation of the manufacturing and assembling process of the instruments before shipping the product to the users. USP categorizes the instruments into Group A, Group B and Group C. The complexity is more towards Group C. Group A instruments are determined by visual inspection which require no independent qualification process. Conformance of Group B instruments are performed according to the standard operating procedures of the respective instruments. Group C includes instruments and computerized analytical systems which are complex and highly complicated which might require assistance of specialists. USP <1058> addresses Software Validation also as the Instrument Control, Data Acquisition and Processing of many of the Group B & C instruments are being done through software. It also addresses the Static and Dynamic documents related to this AIQ process with emphasize on Change Control process to add, delete or revise any of the tests as required.

4 High Level Interpretation of ASTM E ASTM E2500 is a Standard Guide for Specification, Design and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipments. This emerging standard is also applicable to the Laboratory. It is a cost-effective and value added framework focusing exclusively on the critical aspects of the system related to the protection of the patient. This guide emphasis more on the following concepts: Good Engineering Practice (GEP) Science and Risk based approach Process understanding and Continuous Process Improvement Appropriate involvement of relevant Subject Matter Experts (SME) Quality by Design Use of Vendor Documentation Critical Aspects of the Manufacturing Systems Product Knowledge Good Engineering Practice Process Knowledge Regulatory Requirements Requirements Specification and Design Verification Acceptance and Release Operation & Continuous Improvement Company Quality Reqs. Risk Management Design Review Change Management Figure 2 The Specification, Design, and Verification Process Reprinted, with permission, from ASTM E Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, copyright ASTM International, 100 Barr Harbor Drive, West Conshohocken, PA A copy of the complete standard may be obtained from ASTM, Figure 2 summarizes the concepts of the guide at the high level that the requirements are gathered through Product Knowledge, Process Knowledge, Regulatory Requirements and Quality Requirements of the Company with the involvement of Subject Matter Experts and got converted into the Specifications to enable Designing. Once the designing is done, it got verified and released by the Subject Matter Experts after conforming to the predefined specifications. Finally the operation starts with the process for continuous improvement. Good Engineering Practice, Risk Management and Review of the Design are applied throughout the Life Cycle of the entire exercise with appropriate Change Management in place.

5 Aligning ASTM E2500 concepts to USP s AIQ Process ASTM E2500 Analytical Instrument USP <1058> 4Q Model Good Engineering Practice (GEP), Science and Risk based Approach, Process Understanding & Subject Matter Experts (SME) Involvement Risk Management, Design Review & Change Management Requirements Specification and Design Verification Acceptance and Release Design User Specifications Vendor Assessment Installation Operational Performance Change Control Science based Approach Operation and Continuous Improvement Figure 3 Operation & Ongoing Performance Testing Figure 3 provides the holistic view of both ASTM E2500 and USP s AIQ process. If we consider ASTM E2500, the Verification process replaces the processes. But the detailed exercise (IQ, OQ and PQ) might lead to repetitive or additional testing which should be fine from the regulatory stand point. The positive aspects which could be considered for harmonization are, the inclusion of Good Engineering Practice (GEP), Quality by Design (QbD), Use of Vendor Documentation, Science and Risk based approach rather than considering only science based approach, Process Understanding with the Involvement of appropriate Subject Matter Experts and Continuous Process Improvement rather than Operation and ongoing Performance Testing. DQ defines the Functional and Operational specifications based on the intended purpose of the instrument and also the selection criteria for the potential vendor. The manufacturer is responsible for the robust Design and the information related to the manufacturing and testing (Factory Acceptance Testing) of the instruments before shipment. DQ will be performed not only by the vendor but also by the user in some cases. Aligning the ASTM E2500 concepts of Good Engineering Practice, Quality by Design and Use of Vendor Documentation with proper Assessment of the Vendor to have an acceptable Quality System, Technical Capability and evidences for the application of Good Engineering Practice during the development of the product would add value from the regulatory stand point. IQ is the documented collection of activities which verifies delivery as designed and specified, proper installation in the suitable environment. In other words, this is called Site Acceptance Testing. IQ is applicable for the new instruments, existing unqualified ones and in parts when a qualified instrument is relocated or reinstalled. OQ is the documented verification to demonstrate proper functioning of the instrument in the selected environment according to its operational specification. OQ is being performed after installation of the new instrument and after major repair or modification or enhancement, in the case of existing instruments.

6 OQ testing could be of Modular, involving individual components or Holistic, involving the entire system. PQ is the documented verification to demonstrate that the instrument performs consistently according to the specifications and appropriate for the intended use. PQ is performed based on Good Science by analyzing known components or standards to reflect the intended purpose of the instrument as detailed in USP It would be better to adopt a Risk based and Science based approach with proper Risk Assessment by the Subject Matter Experts. It is better to have Risk Assessment for all the Group C instruments as the complexity is more and to some of the Group B instruments as decided by the Subject Matter Experts based on the criticality of the Instrument. PQ tests could also be Modular or Holistic. The testing frequency is fixed based on the criticality of the tests performed and the ruggedness of the instrument. As a harmonized approach, it is better to have the concept of Continuous Process Improvement with the involvement of the Subject Matter Experts throughout the Analytical Instrument process rather than simply having Ongoing Performance Testing. Conclusion The streamlined effort of combining various standards to meet the regulatory requirement as a harmonized approach is an emerging trend. It does not mean that it is not sufficient for an organization to follow Analytical Instrument process as detailed in USP <1058>. Aligning few of the concepts of ASTM E2500 appropriately as detailed in the earlier sections with the USP s AIQ process would definitely result in better regulatory compliance. The individual organizations could achieve this better compliance by considering and incorporating all these concepts while preparing their own policies and procedures related to AIQ process with the involvement of appropriate Subject Matter Experts. References Pharmaceutical cgmps for the 21st Century A Risk Based Approach ASTM E , Standard Guide for Specification, Design and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment United States Pharmacopeia, USP 32 - General Chapter <1058> on Analytical Instrument Process. Dr. Ludwig Huber s Simplify Validation and with ASTM E2500 ICH Q8 Pharmaceutical Development Handbook ICH Q9 Quality Risk Handbook

7 Why HCL? Centre of Excellence for Validation and Compliance Footprint in Global Research driven Leading Pharmaceutical companies Dedicated Industry Managers as resources for the projects being managed in regulated environment RAPS certified consultants Subjected Matter Experts across the Pharmaceutical Value chain with an excellent understanding of business processes. About the Author Navaneetha Kannan Ramachandran, PMP has his Masters degrees in Chemistry and Business Administration with more than 16 years of experience in different Pharmaceutical and IT companies with expertise in multiple functional areas such as Quality Control, Quality Assurance, Analytical Research and Development, Regulatory filings, Quality Audits and Domain Consulting. He has extensive experience in performing different types of Validations with an excellent knowledge in the Systems Life Cycle (SLC) approach for the GxP Critical systems. He is conversant with the requirements of GAMP 5 and ASTM E He has also successfully handled regulatory audits of USFDA/ TGA/ MHRA. He is an HCLite, presently holding the position of Senior Business Manager with the Life Sciences Vertical of HCL Technologies Limited, Chennai, India. He can be reached at navaneethakr@hcl.in.

8 ABOUT HCL HCL Technologies HCL Technologies is a leading global IT services company, working with clients in the areas that impact and redefine the core of their businesses. Since its inception into the global landscape after its IPO in 1999, HCL focuses on transformational outsourcing, underlined by innovation and value creation, and offers integrated portfolio of services including software-led IT solutions, remote infrastructure management, engineering and R&D services and BPO. HCL leverages its extensive global offshore infrastructure and network of offices in 26 countries to provide holistic, multi-service delivery in key industry verticals including Financial Services, Manufacturing, Consumer Services, Public Services and Healthcare. HCL takes pride in its philosophy of Employee First which empowers our 55,688 transformers to create a real value for the customers. HCL Technologies, along with its subsidiaries, had consolidated revenues of US$ 2.5 billion (Rs. 11,833 crores), as on 31st December 2009 (on LTM basis). For more information, please visit About HCL Enterprise HCL is a $5 billion leading global Technology and IT Enterprise that comprises two companies listed in India - HCL Technologies & HCL Infosystems. Founded in 1976, HCL is one of India s original IT garage start-ups, a pioneer of modern computing, and a global transformational enterprise today. Its range of offerings spans Product Engineering, Custom & Package Applications, BPO, IT Infrastructure Services, IT Hardware, Systems Integration, and distribution of ICT products across a wide range of focused industry verticals. The HCL team comprises over 62,000 professionals of diverse nationalities, who operate from 26 countries including over 500 points of presence in India. HCL has global partnerships with several leading Fortune 1000 firms, including leading IT and Technology firms. For more information, please visit