What GMP Documents Does My QMS Need?

What GMP documents are most critical for a small pharma firm’s Quality Management System (QMS)? What role do they play in QMS processes? And which ones should a small pharma firm be most concerned about?

xCellarate Managing Director and Principal Fenton Fong provided insights into GMP documents and QMS processes in the March 30, Redica Systems webinar, “How to Build and Implement a QMS for Small Pharma and Biotech Firms.”

[Related: To view the webinar, including the slide presentation, click here.]

[Author’s Note: Read Parts I and II for more coverage of this webinar.]

When it comes to GMP documents, there is a hierarchy (Figure 1).

“The hierarchy is based on the scope and specificity of each document type in a QMS,” Fong said. The Quality Manual is at the top of the hierarchy as this is the document with the widest scope. It is generally based on ISO. 

So what documents should a small pharma QMS include? The following is a list of documents that should be included in a QMS:

• Master list of controlled documents
• SOPs
• Work instructions
• Templates for the different document types
• Forms
• Registers (signatures, etc.)
• Manuals and policies
• Lists
• Training assessments
• Test methods
• Specifications
• Master manufacturing formula
• Batch records
• Etc.

When it comes to the holistic approach, “you can see how these types of documents play a role in the overall determination of product quality, consistency, and safety in managed risk within the QMS.”

[Author’s Note: For more on GMP documents, view the following clip from the webinar.]

Fong then provided tips for developing effective SOPs. These include using flowcharts/diagrams/pictures and bulleted lists whenever possible, write simply and use verbs to convey what must happen, have a good balance of white space so workers are not faced with heavy blocks of text, avoid inserting version numbers in cited documents, building a consistent template, and require an effective date that is a minimum of 14 days after the approval date.

Rebuilding an Existing QMS

For small pharma firms that already have a QMS, this can be an opportunity to start from a clean slate. He discussed his experience taking an existing QMS and rebuilding it to be more robust. In this situation, Fong recommends the following steps:

1. Create a document management system that includes numbering, version control, and a signature register
2. Train personnel
3. Develop a change control system
4. Draft a Quality Manual
5. Create an SOP on how to write the SOP/template
6. Review vendor management (this is critical for small pharma firms and new companies that rely heavily on suppliers)
7. Write a QA responsibilities SOP

For small pharma companies, it can be challenging to determine where to start when it comes to QMS processes. He has seen this with some of his clients who are unsure which process to start developing for the SOP. Manpower and resources can be an issue as well, particularly during times of rapid growth.

“There are no absolute answers most of the time,” Fong said. “It comes down to a risk assessment and collaborative engagement and agreement with all parties and departments.”

Reviewing agency inspection metrics can also help when rebuilding a QMS. As an example, he pointed to the recent Redica Systems report, FDA FY2020 Drug Inspection Observations and Trends by Barbara W. Unger, one of Redica’s Industry Experts. This report contained a number of insights, notably that the number of FDA 483 observations have steadily increased over the past few years (although they did decrease last year due to the COVID-19 pandemic) and that the top four 21 CFR Part 211 observations from FY2016 to FY2020 usually related to lack of written procedures. 

For a more global look at inspection metrics, Fong reviewed 2019 inspection findings from FDA, MHRA, and Russia’s SID&GP that Redica Systems Senior GMP Quality Expert Jerry Chapman presented late last year. He found that the top three citations concerned data integrity, deviation and failure investigations, and lack of established lab controls, matching up with the findings by Unger. 

Case Study on Mismanaged Stability and Raw Material Release

To show what happens when a firm lacks adequate written procedures, Fong presented a case study on mismanaged stability data and raw material release. In this instance, two batches of the same prescription drug product were seized by a regulatory agency (the company that manufactured the product was under consent decree). 

“If you look closely, you can spot the problem (Figure 2),” he said. “The lot on the right was produced after the batch on the left whereas the assigned expiration dates do not add up.”

An investigation into the batch record for the manufacturing components of both batches found two sources of error. One was a mismanaged stability program and assignment of an incorrect batch expiration date in the instruction for printing. It also was not clear which expiration date was correct. 

“Instead it seemed like both expiration dates were wrong, therefore, casting doubt on both batches,” Fong said.

[Author’s Note: In Part IV, Fenton Fong draws from his experience working with companies in 2020 and also explores the impact of the COVID-19 pandemic on quality management practices.]

[Related: To view the webinar, including the slide presentation, click here.]