PAT in classical process validation!

Hi All,

Looking for opinions on utilization / Allignment of PAT in classical products validation.

Any experience !!

This is what was exactly described in latest process validation guidance by FDA on 11-Jan 2011.
Where ever there is a need of identification of Quality or Inprocess Quality control check PAT will be used.

The major example is during the process validation of a Parenteral Manufacturing (SVP/LVP) or in Manufacturing of a Biological product (Upstream- Down stream-Formulation) rapid microbiological methods are being used to find out the microbiological contamination.
Again for us PAT is working as a tool to identify Risks in above said process as Microbial contamination can occur from any source in this particular Validation process .

RAW MATERIALS (EXCIPIENTS, API’s,Chromatographic Resins,Ultra Filters, Disposables)


FDA’s new paradigm for review and approval of drug submissions now includes creation of a PAT Team approach to joint training, CMC (Chemistry, Manufacturing and Controls ) review as well as cGMP pre-approval inspections (PAIs). The Agency now encourages manufacturers to use PAT to develop mechanistic-based regulatory product specifications. As a way to foster implementation of new analytical technologies in pharmaceutical development and/ or commercial manufacturing, during audits the FDA does not intend to evaluate the suitability of experimental process analyzers or other PAT tools used to gather research information on existing products.

Some of the innovative scientific risk based approaches will come from using new PAT measurement tools
for on- or in-line process analyzers to monitor certain data trends characteristic of a currently acceptable process. FDA has made it clear that routine inspection of a manufacturing process that uses a PAT tool for research purposes will be based on current regulatory standards, for example, test results from currently approved or acceptable regulatory methods. However, under certain circumstances as mentioned in the Compliance Policy Guide Sec. 130.300, the FDA does reserves the right to inspect PAT research data.

Any data, including PAT data, used to support validation or regulatory submissions will be subject to inspection. To reduce some of the uncertainty and anxiety about submitting PAT data for review, the FDA encourages close communication between the manufacturer and the PAT review and inspection team.

To support the PAT initiative, the FDA has developed several systems and practices:
[COLOR=“darkred”]1. Pharmaceutical Quality Assessment Quality Assessment Systems (PQAS) in the Office of New Drug Quality Assessment (ONDQA),
2. Question based review for the Chemistry, Manufacturing and Controls (CMC) evaluation of ANDAs,
3. ASTM standards through Committee E55 on Manufacture of Pharmaceutical Products, and
4. FDA Quality Systems Draft Guidances[/color]

The FDA’s basis of working with ASTM rather than the USP is the objective of National Technology Transfer and Advancement Act, public law 104-113 (NTTAA) of 1996] and the Office of Management and Budget (OMB) Circular A-119 which direct Federal agencies to adopt private sector voluntary consensus standards, when possible, rather than creating proprietary non-consensus standards, such as those from the USP.

One attraction of participating in ASTM is that anyone in the scientific community can participate and write consensus standards. It also has balanced scientific discussion and due process. Furthermore, standards are accepted or rejected by ASTM members by a consensus vote.

Currently there are five approved standards;

[b][COLOR=“blue”]E263-06a (Standard Terminology Relating to PAT in the Pharmaceutical Industry)

E2474-06 (Standard Practice for Pharmaceutical Process Design Utilizing PAT)

E2500-07 (Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment)

E2503-07 (Standard Practice for Qualification of Basket and Paddle Dissolution)

E2537-08 (Standard Guide for the Application of Continuous Quality Verification to Pharmaceutical and Biopharmaceutical Manufacturing).[/color][/b]

Good references from site…thanks.