No Validation, No Controls, and No Suitable Rooms and Equipment - Extensive Warning Letter

Following an inspection in August 2025 at Bio-Medical Pharmaceutical Manufacturing Corporation in Houston, the US Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP). In addition, violations of legal requirements for drug registration and listing were identified. The responses to the inspection findings submitted by the company following the inspection were deemed insufficient by the FDA.

1. Deficiencies in sterile manufacturing and contamination control

The FDA found that the company had not implemented appropriate procedures, equipment and controls to prevent microbiological contamination of drugs intended to be sterile.

Key findings:

• Validated aseptic and/or sterilisation processes were lacking.
• Manufacturing was carried out without appropriate cleanroom classification (e.g. no ISO 5 conditions for aseptic filling).
• There was neither equipment for environmental monitoring nor evidence that such monitoring was performed.
• The production environment was assessed as unhygienic and unsuitable for sterile products (e.g. unclean surfaces, inadequate facility hygiene, unsuitable placement of filling lines).

FDA's conclusion:
The existing facility and process designs are not suitable for ensuring sterility. The corrective measures submitted did not include a sufficient action plan to ensure sterile manufacturing conditions. Therefore, a comprehensive risk assessment of all potential sources of contamination in the aseptic processes, equipment and facilities should be carried out, including an independent assessment. In particular, human intervention in the ISO 5 area, the placement and ergonomics of equipment, air quality, facility layout, and personnel and material flows should be taken into account.

Based on this assessment, a detailed action plan with timelines should be submitted, describing specific improvements to the design and control of aseptic manufacturing operations. In addition, an assessment should be made as to whether terminal sterilisation of the affected medicinal products is possible.

2. Inadequate equipment, process validation and cleaning

The FDA identified comprehensive deficiencies in terms of equipment, process control, validation and cleaning.

a) Unsuitable equipment and system design

• The system used for manufacturing and processing components was structurally unsuitable and inadequately maintained.
• Design flaws (e.g. dead legs and stagnant areas) promoted biofilm formation and microbial growth.
• There was a lack of adequate validation, maintenance, microbiological monitoring and testing concepts.
• The proposed corrective measures did not include complete replacement and revalidation of the system.

b) Lack of process validation

• There were insufficient qualifications for equipment and processes.
• The validation evidence submitted for sterilisation processes was assessed as fundamentally flawed.
• Important elements of validated sterile manufacturing (e.g. suitable environmental conditions, robust process controls, sterility testing of batches) were missing.
• Manufacturing processes were not validated or monitored throughout the entire life cycle.

c) Lack of cleaning validation and risk of cross-contamination

• Sterile and non-sterile products as well as cosmetics were manufactured on non-dedicated equipment.
• There were no validated cleaning procedures in place to demonstrate reliable removal of residues and active ingredients.
• The disinfection procedures used did not include validated parameters such as contact times, concentrations or residue controls.
• This posed a significant risk of cross-contamination between products.

FDA assessment:
The company did not have a robust validation, maintenance and cleaning programme in place to ensure consistent product quality. The company is required to submit a comprehensive corrective action plan (CAPA) that ensures effective monitoring of facilities, equipment and manufacturing processes. This includes, in particular, improvements in maintenance, servicing, technical equipment and management controls. In addition, a detailed remediation and validation plan for the system used must be submitted, including new validation reports, microbiological limits, possible endotoxin tests and a risk analysis for batches already on the market. Furthermore, the FDA requires a complete validation programme covering the entire product life cycle, including schedules for process qualifications, risk analyses for products already manufactured, and programmes for the qualification of equipment and processes.

Finally, the company must submit a revised cleaning and disinfection plan, including cleaning validation, worst-case scenarios, process improvements, and updated SOPs and change management requirements for new equipment or products.

3. Inadequate quality control and release testing

The FDA found that the company did not perform adequate laboratory testing for batch release.

Key findings:

• Sterility testing for sterile products prior to batch release was lacking.
• Non-sterile products were not adequately tested for microbiological contamination. 
• Chemical and microbiological final testing was incomplete or inadequate. 
• Test methods and parameters (e.g. media, incubation conditions, sample size) were not adequately validated. 
• No retrospective risk analysis was performed for batches that had already been released without adequate testing.

FDA assessment:
Without complete release testing, there is insufficient scientific basis to ensure the quality, safety and compliance of the products. The company is to conduct a comprehensive, independent assessment of its laboratory system (including procedures, methods, equipment, documentation and staff qualifications) and, based on this, submit a detailed improvement plan.
In addition, a complete overview of the chemical and microbiological specifications and test methods for batch release must be submitted. Furthermore, the FDA requires an action plan with a timeframe for complete retesting (chemical and microbiological) of retention samples of all batches still in shelf life and distributed in the US, as well as a summary of the test results. If quality defects are found, measures such as customer notifications or product recalls must be initiated immediately.

4. Violations of drug registration and listing

The FDA found that a manufactured drug was not properly reported in the electronic registration system. This constitutes a violation of legal reporting requirements and may have implications for inspections, supply chain security and market surveillance.

5. Recall and suspension of distribution

Following discussions with the FDA, the following recommendations were made:

• Removal of affected products from the US market.
• Suspend further distribution.

6. Recommendation to hire an external CGMP consultant

Due to the severity and systematic nature of the deficiencies identified, the FDA recommended engaging a qualified external consultant to comprehensively evaluate the quality systems and implement effective CAPA measures. However, responsibility for compliance with regulatory requirements remains with the company's management.

7. Information on cosmetic products

In addition, the FDA pointed out that cosmetic products manufactured by the company must also comply with the applicable legal requirements and the new provisions of the Modernization of Cosmetics Regulation Act (MoCRA).

The complete warning letter with further details can be found on the FDA website.