Process Validation
“Process Validation is the documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or API (active pharmaceutical ingredient) meeting its predetermined specifications and quality attributes.” (Quote ICH Q7)
Defined in guideline ICH Q7 “Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients”. ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use)
Biologicals and ATMP Manufacturing
Why Process Validation?
Process validation for biologicals is a lifecycle and risk-based scientific approach proving that a manufacturing process consistently produces biological products meeting predetermined quality and safety standards.
Because end-product testing of biotechnological-derived products is of limited practicality, the validation of the manufacturing process is demanding regarding the complexity of biopharmaceuticals and immunotherapies.
Quality Compliance
GMP compliance
- The objective of process validation is to ensure product quality, in terms of safety and efficacy, and that products are being consistently produced and controlled to the quality standard appropriate to their intended use and as required by regulatory authorities for GMP release (21 CFR 211.100 and 21 CFR 211.110).
Process Specifications
- Considering the complexity of biopharmaceuticals and that full product characterization is rather difficult to achieve, specifications are part of quality control (ICH Q6B).
- Specifications are critical quality characteristics. Validation parameters and acceptance criteria are part of the in-process controls. The quality control unit is responsible for the establishment of scientifically sound and appropriate specification standards, sampling plans, and test procedures.
- The objective of specifications is to ensure product and process quality in terms of “batch-to-batch” consistency and compliance to good manufacturing practices (GMP).
- The FDA requirements are stated in the code of federal regulation 21 CFR § 211.160.
Risk Analysis
- Critical quality attributes (CQAs) and critical process parameters (CPPs) play a key role within your risk assessment.
Audits and Inspections
- Regulatory authorities such as FDA or EMA have the authority and responsibility to inspect and evaluate process validation. The manufacturer is in charge to perform and implement process validation. FDA and the European Medicines Agency (EMA) represents “Guidelines on Process Validation”.
Statutory FDA Requirements
The FDA requires that the medicinal product meet the safety aspects, and the identity, strength, purity, and quality specifications which it states to have, as required by section 501(a)(2)(B) of the act.
Food, Drug, and Cosmetic Act (FD&C Act) Section 501 (a)(2)(B)
A drug is deemed adulterated if its manufacturing, processing, packing, or holding method do not conform to cGMP to ensure safety, quality, and purity.
(a) Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act provides that a drug (including a drug contained in a medicated feed) shall be deemed to be adulterated if the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirement of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.
GMP Regulations and Guidance
- FDA Guidance for Industry: Process Validation
- FDA Guidance for Industry: PAT
- FDA Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP regulations
- EMA – Process validation for the manufacture of biotechnology-derived active substances
- EMA – Guideline on process validation for finished products
On-site Services
- Validating Manufacturing Process
- Assisting Upstream and Downstream Operations
- Applying Microbiology and Hygiene Concepts
- Validating Aseptic Processes (Annex 1)
Key Benefits
Our validation engineers at Stolley Engineering, who are well-qualified, have an understanding of biopharmaceutical science, critical process parameters (CPPs), critical quality attributes (CQAs) and the manufacturing process related to biopharmaceuticals and immunotherapies, allowing us to determine and define process specifications and their acceptance criteria.
