Quality Assurance and Quality Control in Generics Dr. Tara Jayaram 13th Oct. 2017

My Profile Ph.D from Bangalore University (Biochemistry and Microbiology). 20 Years as Head of Quality and Regulatory Affairs at Biocon Limited. Management Representative and Management Appointee for ISO 9001, ISO 14001 and OHSAS 18001. 06 Years as Head of Quality and Regulatory Affairs at Syngene International Limited: GMP: QC, QA, RA, GLP: Management, GCP: QA. 02 Years as Head of Technical Training at Mylan Laboratories Limited. Current – Consultant in Quality Systems (GMP, GLP, GCP, ISO).

What is a Generic Drug? A generic drug is a copy of the Brand name drug: Same quality Same safety Same strength FDA assures that Generics: Are safe, effective, FDA approved Are an affordable alternative Can be used with confidence Both Brand name drug and Generic drug: Should be approved by FDA Must meet the same FDA standards for quality

Generic Drug Generic drugs must : Contain the same active ingredient at the same strength as the "innovator" drug. Be bioequivalent. Meet the same pharmacopoeial standards as applicable. Be identical in dose, strength, route of administration, safety, efficacy, and intended use.

Generic Drugs Companies - Responsibilities The Generic drug company must: Fully document the Generic drug’s Chemistry, Manufacturing steps and Quality Control measures. Ensure that the raw materials and finished products meet USP specifications, if these have been set. Show that the Generic drug maintains stability as labelled before it is sold. Continue to monitor the stability of the Generic drug.

What is Quality? Quality is an important factor when it comes to any product. Therefore all manufacturers constantly look for enhancing the quality of their product. Quality is the totality of features and characteristics of a medicinal product and its ability to satisfy stated and / or implied needs

Quality - Definition Quality in manufacturing is a measure of excellence or a state of being free from defects, deficiencies and significant variations. Quality is brought about by strict and consistent commitment to certain standards that achieve uniformity of a product in order to satisfy specific customer or user requirements.

The Five M’s of Quality Man Material Machinery Manuals / Methodology (SOPs) Motivation

Quality - Techniques In order to maintain or enhance the quality of the product, the manufacturers use two techniques : Quality Control and Quality Assurance. These two techniques through GMP ensure that the end product meets the quality requirements and standards defined for the product.

QA & QC - Definition Pharmaceutical Quality Assurance (QA)—Sum of all activities and responsibilities required to ensure that the medicine that reaches the patient is safe, effective and acceptable to the patient. Pharmaceutical Quality Control (QC)—Process concerned with medicine sampling, specifications, testing and with the organization’s release procedures that ensure that the necessary tests are carried out and that the materials are not released for use, nor products released for sale or supply, until their quality has been judged satisfactorily.

GMP Good Manufacturing Practices (GMP)—Performance standards established for pharmaceutical manufacturers covering, for example, personnel, facilities, packaging and Quality Control. GMPs are part of the Quality Assurance activities that ensure that products are consistently produced and controlled to the quality standards appropriate to their intended use and required by the drug regulatory authorities.

Quality Assurance - Definition Is a dynamic process and it is a journey towards the final destination. Is process oriented and focuses on defect prevention. Is a set of activities for ensuring quality in the processes by which products are manufactured. Is all those planned and systematic actions necessary to provide adequate confidence that the product will fulfil the requirements for quality.

Quality Assurance (QA) - Goal The goal of QA is to improve the manufacturing processes and test the processes so that defects do not arise during the manufacturing processes. To achieve QA goals: Establish a good quality management system and the assessment of its adequacy. Periodic conformance audits of the operations of the system to ensure compliance of the system. Prevention of quality problems through planned and systematic activities including documentation.

Quality Assurance - Role A process and not an end point. Must be independent of financial pressures. Must ensure that set quality processes are followed. Must have final authority in product acceptance, rejection and release to public. Integral to production and not an add on. Responsible for day-to-day operations and for longer term goal setting.

Quality Assurance - Role Ensures that all process control operations are well defined in written form and GMP requirements are adopted. Ensures usage of correct starting and packaging materials. All necessary controls on starting materials, intermediate products, bulk products and other in process controls, calibrations, qualifications and validations are carried out.

Quality Assurance - Role Ensures that the finished products are correctly processed and checked to the defined procedures and specifications. Ensures that Products are not sold or supplied before the authorised persons have certified that each production batch has been manufactured and controlled in accordance to GMP requirements. Regular evaluations of the product quality is conducted with the objective of verifying the consistency of the process and ensuring its continuous improvement through Annual Product Review. Complaint handling. Documentation of the process from the starting material till the end user and its storage throughout. Stability studies as per regulatory requirement / customer requirement.

Quality Assurance - Activities Technology transfer Validation and Qualification Documentation Assuring quality of products Quality improvement plans

Quality Assurance - Activities Technology transfer: Receipt of product design documents from RND. Receipt of the trial and error data and its final evaluation (development report). Checking and approval of documents based on RND data – Batch Manufacturing Records. Scale-up and validation of the process / product.

Quality Assurance - Activities Definition of Validation: Action of proving (in accordance with principles of GMP) that any procedure, process, equipment, material, testing or system actually leads to expected results. Validation: Preparation of Master Validation Plan for Facility, Equipment, Process Utility, Cleaning and all sections of the validation. Approval of validation protocols. Selection of validation team to carry out validation. Final approval of all validations. Qualification: Action of proving that any premises, system and equipment work correctly and actually lead to expected results.

Quality Assurance - Activities Review and Approval of Documentation: SOPs Protocols Results Reports Laboratory records Documentation control and approval

Quality Assurance - Activities Assuring Quality of products through: cGMP training SOP compliance Audit of facility and systems for compliance Line clearance In-process checks Record verification Release of batch for marketing Investigation of market complaints.

Quality Assurance - Activities Quality Improvement Plan through: Feedback received from compliance team. Customer complaint history. Proposals for corrective and preventive actions. Annual products review. Trend analysis of various quality parameters for products, environment and water. Review of the deviations, change controls, out of specifications and failures / rejections.

Quality Control - Definition Quality Control is product oriented and focuses on defect identification. Quality Control is a set of activities for ensuring required quality in the product. The activities focus on identifying defects in the actual products manufactured. Quality Control functions start as soon as the product manufacturing begins. Quality Control is a reactive approach and helps in identifying the defects in the deliverables.

Quality Control (QC) - Goal The goal of QC is to identify the defects after the products are manufactured and before it is released for distribution. To achieve QC goals: Finding and eliminating quality problems through tools and equipment so that customer’s requirements are continually met. The activities or techniques used to achieve and maintain the product quality, process.

Quality Control - Role Evaluation of Quality throughout the manufacturing process: Raw materials, excipients and API In-process samples Drug Product Packaging components Re-assay Retains Stability

Quality Control - Role Evaluation of Quality throughout the manufacturing process: Analytical Method Validations Process Validations Cleaning Validations Quality Compliance

Quality Control - Activities Establishing: Specifications, Protocols and Reports. Developing: Analytical Methods. Qualification and Calibration of Laboratory Equipment and Instruments. Analyses of samples as per specifications. Preparation of Certificates of Analyses.

Quality Assurance (QA) & Quality Control (QC) QC & QA - Working together: QC detects a problem with the product during manufacture or after the manufacture. QC provides a feedback to QA about the problem in the process or the system which is resulting in product quality problems. QA determines the root cause of the problem and then brings changes to the process to ensure that there are no quality issues in future.

The Differences between QA and QC QA plans to avoid defects. QA is all about prevention of problems. QA is a process based approach. QA involves in processes managing quality. QC QC tries to find defects and correct them while manufacturing the product. QC is all about detection of problems. QC is a product based approach. QC involves in verifying the quality of the product.

The differences between QA and QC QA conducts quality audits to ensure that the processes are manufactured as per requirements. The goal of QA is to develop a robust process so that defects do not arise when the product is being manufactured. QC QC conducts testing of the product to ensure that the required quality parameters are met. The goal of QC is to identify the defects when the product is manufactured before it is released.

The benefits of QA and QC Manufacturing a high quality product. Increases the efficiency of the operations. Brings in customer satisfaction which helps in business growth. Reduces or stops rework which helps in cost saving of the process.

Conclusion THANK YOU To ensure customer satisfaction: Plan the manufacturing process. Have a motivated team to manufacture, test and release. Follow GMP throughout the process including manufacturing and testing. Have an independent QA with full authority for the product release. Deliver the product to the customer on time. THANK YOU