Significant Deficiencies in Microbiological and Analytical Quality Control

In July 2025, the US Food and Drug Administration (FDA) inspected the drug manufacturing facility of Fulijaya Manufacturing SDN. BHD. in Kulim, Malaysia. Significant violations of Current Good Manufacturing Practice (CGMP) were found in accordance with Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211 for finished medicinal products. Due to inadequate manufacturing, testing and quality assurance processes, the FDA considers the manufactured medicinal products to be ‘adulterated’ within the meaning of the US Federal Food, Drug, and Cosmetic Act (FD&C Act) Section 501.
The FDA reviewed the company's response of 20 August 2025, but found that the identified deficiencies were not addressed sufficiently in the responses and planned actions.

1. Deficiencies in laboratory records and data integrity

The company did not ensure that laboratory records contained complete and original data for all required tests. For example, raw data and logbooks for microbiological release and stability tests prior to May 2025 could not be provided.
The FDA emphasises that missing or incomplete data significantly compromises the reliability of analyses and the ability of quality control to ensure product quality. In the agency's view, the quality system does not ensure the necessary data integrity to support the safety, efficacy and quality of medicinal products, as outlined, for example, in the FDA's Guidance ‘Data Integrity and Compliance With Drug CGMP’.
The FDA demands:

• A comprehensive investigation of the extent and causes of data integrity deficiencies.
• A risk assessment of possible effects on patients and product quality.
• A company-wide strategy for corrective and preventive actions (CAPA) to ensure complete and reliable data.

2. Inadequate laboratory and microbiological controls

The company was unable to demonstrate that its microbiological testing methods are suitable for ensuring product quality and purity. Among other things, the following were identified:

• Lack of growth promotion tests (GPT) for microbiological culture media prior to their use.
• Inadequate testing of components for relevant microorganisms such as Burkholderia cepacia complex (BCC).
• Reliance on supplier certificates such as CoA without independent verification. A suitability test, e.g. for BCC, was not performed.

The FDA assessed the company's response as insufficient, as the internal microbiological data was not reliable due to faulty methods, meaning that the non-validated or non-verified testing methods posed a risk to consumers.
The following are therefore required:

• An independent, comprehensive assessment of laboratory practices, methods and competencies.
• Validated specifications and test methods for chemical and microbiological analyses.
• Re-testing of retained samples of all batches still on the US market.
• Retrospective risk assessment of the suitability of culture media and microbiological tests in recent years.
• Immediate action, such as customer information and recalls, in the event of identified quality defects.

3. Inadequate stability programme

The company did not have sufficient stability data to demonstrate that the quality characteristics of the products would be maintained throughout the declared shelf life.
Deficiencies included, among others:

• Lack of active ingredient analyses at all intended stability time points.
• No defined limits or tests for impurities.
• Incomplete stability data that did not cover all active ingredients and impurities.

4. The FDA requires:

• A comprehensive independent assessment and a CAPA plan to improve the stability programme.
• Stability-indicating methods and studies for each product in the final packaging system prior to marketing.
• An ongoing stability programme with annual inclusion of representative batches.
• Clear definition of all quality attributes to be tested and timepoints.

5. Use of external testing laboratories and manufacturer responsibility

The FDA points out that contracted testing laboratories are considered an extension of the manufacturer and must fully comply with CGMP requirements. The manufacturer remains responsible for validating the methods used and the quality of the ingredients used. A comprehensive evaluation of all tests performed by contract laboratories is required.

Quality systems and management responsibility

The company's quality system is therefore rated as insufficient overall and external consultation is recommended to remedy the situation. Further details can be found in the Warning Letter an Fulijaya Manufacturing.