10 Overlooked Questions for Drug Manufacturing Inspection Readiness
A practical guide drawn from the FDA Compliance Manual, our audit experience, and common pitfalls that sink compliance efforts.
The FDA Compliance Program 7356.002, Drug Manufacturing Inspections, is the agency's blueprint for evaluating whether pharmaceutical manufacturers operate under control.
This 44-page document, issued under Chapter 56, Drug Quality Assurance, outlines inspectors' risk-based, systems-oriented approach to assessing compliance with CGMP requirements.
This isn't just another regulatory checklist—it's the standard by which your manufacturing processes are judged. The problem? Most compliance failures aren’t the obvious ones. While firms focus on ticking off the obvious CGMP requirements, it's the overlooked details—the blind spots in processes, quality oversight, and documentation—that most often trigger FDA findings.
This guide distills the ten most commonly overlooked compliance questions that can make or break an inspection. Each section draws from FDA inspection manuals, ICH guidances (Q9, Q10, Q12), and real-world enforcement trends to highlight:
What the FDA is actually looking for.
The hidden compliance gaps firms frequently miss.
Practical, actionable steps to stress-test your processes before the FDA does.
If your team cannot answer these ten questions confidently, your operation isn’t inspection-ready. Use this guide as a pre-audit checklist to identify weaknesses, eliminate risks, and ensure your facility meets the FDA’s evolving expectations before they show up at your door.
Also, be sure to catch our recent sit-down with Divya Gowdar, Founder and CEO of NubGenix, where we discussed the pitfalls and lessons learned on the frontlines of audit and inspection readiness throughout the FDA-regulated industries:
1. Is senior management actively leading quality initiatives, or have they fallen into rubber-stamping compliance?
The FDA doesn’t just want leadership to sign off on compliance reports—it expects them to own product quality. The compliance manual makes it clear: management must be involved in setting quality strategy, not just reacting to problems. This means having a documented quality policy that drives real decisions, not a boilerplate statement that sits in an SOP binder.
One best practice is to implement quarterly Quality Management Review meetings that go beyond a checklist exercise. These meetings should analyze trends in CAPAs, batch rejections, and deviations, then outline concrete actions for improvement. Instead of relying on a static set of KPIs, firms should ask:
Are we seeing repeat deviations?
Are CAPAs actually fixing the root cause or just addressing symptoms?
How often does management challenge the effectiveness of the quality system?
Our audit projects often uncover situations where senior management lacks active engagement in quality decision-making. One recurring theme is that the quality system looks solid on paper, but in practice, management is detached from ongoing quality performance. If leadership is merely signing off on reports without diving into real data, expect auditors and the FDA to raise red flags.
2. Are we aggressively identifying and eliminating impurity risks (e.g., nitrosamines) throughout production?
The FDA has intensified its scrutiny of nitrosamine impurities and genotoxic contaminants, holding manufacturers accountable for proactively identifying and mitigating risks. This isn’t just about testing the final product—it’s about having a lifecycle risk management strategy that prevents impurities from forming in the first place.
Firms should be conducting comprehensive impurity risk assessments across the entire supply chain. This means evaluating:
API synthesis pathways: Could conditions (temperature, catalysts) lead to impurity formation?
Excipients and packaging: Could plasticizers or stabilizers leach harmful byproducts into the drug?
Storage and distribution: Could humidity or temperature excursions accelerate impurity formation?
A common failure our auditors (and FDA investigators) find is firms relying on supplier COAs without independent verification.
In one recent example, a company assumed its API was free from nitrosamines because the supplier provided a clean COA. An audit revealed they never tested it themselves, and later, a batch was found contaminated. The best practice? Do your own confirmatory testing—don’t assume upstream controls are foolproof.
3. Can our facility layout and air handling system prevent cross-contamination?
Airborne cross-contamination is one of the top reasons facilities fail inspections. The compliance manual states that firms must validate their air handling, pressure differentials, and physical separation strategies—especially for high-risk drugs like hormones, beta-lactams, and cytotoxic.
A strong facility design should include:
Dedicated manufacturing areas for high-potency drugs.
HVAC validation with airflow mapping to prevent contamination drift.
Real-time monitoring of differential pressures and air quality.
In one of our recent audits, we discovered that an HVAC system failed to maintain proper airflow separation within a site manufacturing both cytotoxic drugs and general pharmaceuticals.
Ask yourself:
Can we prove our air handling system prevents contamination?
When was the last time our HVAC validation data was updated?
Are we tracking particulate and microbiological contamination levels?
If you’re relying on old airflow validation data or assuming that physical barriers alone prevent contamination, you’re taking a huge compliance risk. The manual explicitly instructs investigators to probe deep here.
4. Are our equipment cleaning validation protocols scientifically sound and consistently reassessed?
Our auditors frequently catch firms cutting corners on cleaning validation—especially when manufacturing multiple products on shared equipment. The FDA’s compliance manual is clear: firms must validate that equipment cleaning removes all residues before switching to a new product.
Here are a few best practices that should be obvious, but we see go ignored way too frequently:
Swab and rinse sampling at worst-case locations (gaskets, agitator shafts, dead legs).
Use of Total Organic Carbon (TOC) testing to detect trace residues.
Periodic revalidation of cleaning methods, especially after equipment modifications.
Here’s a classic audit failure that commonly appears in the reports we prepare: companies rely on visual inspection alone to confirm cleanliness. You cannot simply “look” at equipment surfaces and declare them clean without chemical confirmation. This is how cross-contamination between batches enters the market (and also results in embarrassing warning letters).
5. Do we independently verify supplier-provided raw materials and packaging test results?
A supplier’s COA is not a quality guarantee—it’s just a statement. The FDA’s compliance manual instructs investigators to ensure that firms independently verify raw materials through at least one identity test. Yet many, many firms skip this step, trusting COAs at face value in the interest of time and energy. Our recommendations:
Conduct FTIR, HPLC, or mass spectrometry on incoming raw materials.
Audit suppliers annually—don’t just trust paperwork. (Talk to us if you need to schedule your supplier audits this year.)
Cross-check supplier test data against historical results for variability.
One firm we recently embedded into had skipped identity testing for an excipient because the supplier “had a good reputation.” An FDA inspection later found that the excipient contained undeclared impurities.
Ask yourself:
Are we trusting supplier COAs without verification?
Do we challenge our suppliers’ quality data?
If an ingredient failed, would we catch it before it reached production?
6. Is our computerized inventory control system validated and audit-ready?
Digital inventory tracking is a double-edged sword. It’s efficient, but it also creates compliance risks if not properly validated. The FDA expects firms to have fully validated inventory systems that provide:
Automated tracking of raw materials and expiration dates.
Audit trails that capture every inventory movement.
Alerts for missing or outdated materials.
Many firms get cited for manual overrides in inventory systems that allow expired materials to be used. In one recent warning letter, a firm had a computerized inventory system that let operators manually change expiration dates—leading to expired raw materials being used in production.
The questions to ask yourself here:
Can our system trace every raw material from receipt to final product?
Are manual changes logged and reviewed?
Have we validated our inventory software’s ability to prevent compliance gaps?
7. Are our in-process control limits scientifically justified or just historical artifacts?
Many manufacturers inherit in-process control limits from historical data rather than setting them based on current process capability. The FDA expects firms to apply statistical process control (SPC) to detect variability before it leads to deviations. If your process limits are static and haven’t been reassessed using current process data, you're leaving gaps that could cause compliance failures.
A best practice we typically prescribe is calculating the Process Capability Index (Cpk/Ppk) to assess whether critical process parameters consistently meet specifications. A Cpk of 1.33 or higher indicates a stable process, while lower values suggest a high risk of variability and drift. You should trend your blending uniformity, granulation particle size, and tablet compression forces to catch deviations before they result in an OOS batch.
A common audit failure occurs when firms adjust control limits reactively after a deviation instead of conducting proactive trending analysis. More than once we’ve found firms failing to detect a slow drift in tablet hardness over multiple batches—an issue that could have been caught earlier with proper SPC monitoring.
Key self-check:
Are our process control limits based on statistical validation or just legacy numbers?
Do we trend in-process data or only react to OOS failures?
Can we demonstrate Cpk/Ppk values for critical process parameters?
8. Do we have an active control strategy for preventing hazardous impurities during manufacturing?
The FDA doesn’t want manufacturers to just test for impurities—it wants firms to actively prevent them using real-time monitoring and process controls. This means having a control strategy that integrates:
Process Analytical Technology (PAT) to monitor reaction conditions (pH, temperature, moisture) in real time.
Worst-case scenario modeling to assess impurity risks in abnormal conditions.
Routine impurity trending analysis to catch patterns before they result in failures.
Many firms rely solely on finished product testing to catch impurities, but by then, it’s too late.
Do you have real-time monitoring for impurity formation risks?
Have you modeled your worst-case impurity formation scenarios?
Are you trending impurity levels to identify early warning signs?
9. Are our labeling controls preventing mix-ups and reconciliation errors?
Mislabeling is a major cause of pharma recalls—and it’s often preventable. The FDA requires manufacturers to have strict label reconciliation and verification processes to eliminate the risk of mix-ups. This is especially critical for products with similar packaging, different strengths, or different formulations within the same brand family.
A strong labeling control strategy includes:
100% barcode scanning or vision inspection at multiple points in the packaging process.
Strict reconciliation of issued and unused labels—unused labels must be accounted for and destroyed.
Line clearance verification between batches to prevent rogue labels from being carried over.
A common pitfall is relying on manual label checks, which are prone to human error. In one audit, we found that a firm stored labels in open bins near the packaging line, leading to an inadvertent mix-up.
Areyou tracking every label issued and used?
Do you rely on automation and scanning, or just manual checks?
Have you implemented line clearance checks between production runs?
10. Are our out-of-specification (OOS) investigations thorough, scientifically justified, and fully documented?
An OOS investigation is one of the first things an FDA inspector will scrutinize. If your process for handling OOS results is weak, expect it to be called out immediately. The FDA requires OOS investigations to follow a structured, root-cause-driven approach, ensuring that failures are addressed scientifically.
The best approach to OOS investigations follows a three-phase process:
Phase 1: Confirm the validity of the result. Retest to rule out lab errors, instrument malfunctions, or sample handling issues.
Phase 2: Investigate potential lab-based errors. If no lab issues are found, assess operator variability, testing conditions, and analytical method performance.
Phase 3: Assess process-related failures. If the test is confirmed valid, trace it back to manufacturing root causes—raw material variability, processing deviations, or equipment malfunctions.
A common FDA finding is that firms prematurely close OOS investigations without actually finding the root cause.
Are you systematically identifying root causes or just looking for quick resolutions?
Do you follow a structured, multi-phase OOS investigation process?
Are you tracking OOS trends across different batches to identify recurring issues?
Are you ready for your next FDA inspection?
If you’re unsure whether your team could confidently answer these ten critical compliance questions, now is the time to act. Many firms assume they’re compliant—until an FDA inspection proves otherwise. The key to avoiding enforcement actions isn’t just having SOPs in place; it’s making sure they’re fully integrated, continuously improved, and demonstrably effective.
At The FDA Group, we help pharmaceutical manufacturers and suppliers eliminate compliance blind spots before they become regulatory liabilities. Our experts—former FDA investigators and seasoned industry professionals—bring insider-level inspection expertise to help you:
Conduct in-depth audits and mock inspections based on real FDA inspection methodologies.
Strengthen OOS investigations, labeling controls, and impurity prevention strategies.
Prepare senior leadership to drive continuous quality improvements.
Compliance isn’t static—it’s a moving target. The companies that stay ahead aren’t waiting for the FDA to find gaps—they’re actively identifying and fixing them first. Drop us a line to start the conversation.
Who is The FDA Group?
The FDA Group helps life science organizations rapidly access the industry's best consultants, contractors, and candidates. Our resources assist in every stage of the product lifecycle, from clinical development to commercialization, with a focus on Quality Assurance, Regulatory Affairs, and Clinical Operations.
With thousands of resources worldwide, hundreds of whom are former FDA, we meet your precise resourcing needs through a fast, convenient talent selection process supported by a Total Quality Guarantee. Learn more and schedule a call with us to see if we’re a fit to help you access specialized professionals and execute your projects on time and on budget.