According to, more than 408,395 clinical trials are being conducted in 50 states and about 220 countries. About 53,000 of these studies are in early or clinical phase 1, 22,000 in clinical phase 2, and 5,000 in clinical phase 3, representing different stages of product development.

While the major focus of pharma professionals developing early clinical trial materials is on R&D, it is important to note that good manufacturing practices (GMP) implementation is, at some level, equally important in the early phases.

Taking it a step further, it’s important for professionals to not only consider GMP implementation throughout the early stages, but also other good practice quality guidelines.

ICQ CQV experts conducting product development research

The failure rate of clinical trial outcomes is upward of 50%. Could the excessive failure rate be because of this lack of challenge to the process in general and R&D in particular? The answer could be yes, as the “how” and “why” of the R&D phase and GxP is rarely audited.

The question should be, when was the last time expert quality personnel audited the process at each stage? What about a combined audit from the receipt of raw material to clinical trials, material release, and subsequently, to clinical outcomes?

If the answer is “never” or “not on a regular, controlled, and documented basis,” a company may be in for surprises when they see the data generated so far.

When to Start Thinking About GxP?

The plain and straightforward answer is from the start of the product development.

The common perception of not needing to consider GxP for phase 1 and preclinical studies is misleading, partly confused by the 21 CFR 210 final rule, which states that 21 CFR Part 211 does not apply to investigational drugs for use in phase 1 studies.

While GMP may not be a requirement in this particular situation, developers creating a product intended for human use will need to consider other GxP requirements, regardless of its development phase.

The difference in the degree of GxP depends on how much knowledge is acquired about the product as it moves from preclinical to phase 1, phase 2, phase 3, and then to commercial.

9 Critical GxP Parameters

To promote a trouble-free process from start to finish, here are nine critical GxP parameters to pay attention to throughout the different phases of development:

  1. Use calibrated equipment and set up a strong equipment maintenance program starting during R&D and finalize it before phase 1 development.
  2. Ensure the proposed design of the facilities, utilities, and equipment suits the intended purpose. Initiate design review and qualification before shipping systems/equipment to the site.
  3. Qualify analytical methods at the pre-clinical (Tox) phase with qualification completed by phase 1.
  4. Analytical method validation shall proceed from phase 1 and continue into phase 3 as more information accumulates during product development.
  5. Qualify systems and equipment for phase 1 development use, with the risk and criticality assessments completed at the beginning of this phase.
  6. Set up Bioburden and Endotoxin Controls at the beginning of phase 1 development and continue into the biologics license application (BLA) submission phase (phase 2b or 3) as you collect more information about the product.
  7. Process validation shall begin at the start of the BLA submission phase and be completed before the end.
  8. Utilize good clinical laboratory practices (GCLP) at all stages of clinical testing.
  9. Implement data integrity procedures, as required by GMP, at all stages of development to ensure data is complete, consistent, and accurate.

Ensure Smooth Sailing

The time to keep clinical trials outcomes separate from development, manufacturing, and quality control departments is over as biotech products are susceptible to minor chemistry, manufacturing, and controls (CMC) changes.

The distinct phases of clinical trials and development are fading as we enter the world of biotech products, where we use cohort studies for BLA submissions in phase 2.

While the GxP rules ensure patient safety by design, let us not miss out on the opportunity these rules give us to ensure smooth sailing from development to approval.

Written By: Abdul Zahir, Senior Consultant

PDA Technical Report 56

EudraLex Volume 4

21 CFR Parts 210, 211, 600

International Committee on Harmonization (ICH) Q8, Q9, Q10

Analytical Procedures and Methods Validation for Drugs and Biologics: July 2015

FDA Quality Issues for Clinical Trial Materials: The Chemistry, Manufacturing and Controls (CMC) Review

ASTM International – Designation E2500-07