1.5 Regulations Summary

3P ENTERPRISE

Compendial environmental monitoring

Automated method

The special feature of the 3P solution is that it's not an alternative method, but an automated one: automatic reading instead of manual reading.

SCANRDI

Alternative Sterility Method

Still only known as an alternative method even if several texts are currently under development as described below: US: The specific guideline for sterility testing for short-life sterile products is USP <1071>. A new mandatory one dedicated to cytometry approach is on going major revision: USP <74> for the detection of Contamination in Short Life Products

Full validation of a rapid sterility test must demonstrate its equivalence (or superiority) to the compendial method.

GMP ANNEX 15

GMP is MANDATORY governed by 21 of the Code of Federal Regulations explaining what to do. This Annex describes the principles of QUALIFICATION and VALIDATION which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II.

Notice: GMP can also be called cGMP for current GMP

BACT/ALERT 3D

Alternative Sterility Method except for Short Life Product in some regions

Full validation of a rapid sterility test must demonstrate its equivalence (or superiority) to the compendial method (Ph. Eur. 2.6.1 / USP <71> / JP 4.06).

Full validation of a rapid sterility test must demonstrate its equivalence (or superiority) to the compendial method. Notice that for Short-shlef life product, USP<1071> give some adapted guidelines.

3P ENTERPRISE

Automation of customer's Environmental Monitoring process

The special feature of the 3P solution is that it's not an alternative method, but an automated one. BUT If the customer changes his process as:

• Single temperature or
• Shorter incubation time,

Then the method becomes alternative.

ENDONEXT Solution

Alternative & Compendial endotoxine detection

The current compendial method for the detection of endotoxin is the LAL Method, using blood cells from Horseshoe crab compare to ENDONEXT™ Endotoxin Detection Assays which is based on recombinant Horseshoe Crab Factor C (rFC).

The rFC approach gaining acceptance in many regions being more and more compendial.

ENDONEXT solution

Compendial in EUROPE and soon in US

• EUROPE: EP 2.6.32
• US: USP <86>

ALTERNATIVE APPROACH

Identification ranges

USP<1113> "MICROBIAL CHARACTERIZATION, IDENTIFICATION, AND STRAIN TYPING"

The special feature of these ranges is that the method never involves the customer's product.

There is never any question of Method suitability testing or non-interference. To verify these methods, the parameters listed in the texts relating to alternative methods must be assessed, such as Sensitivity, Specificity, Reproducibility...

BACT/ALERT 3D

The range that is compendial according to the most widespread texts in the world but only for short shelf life products.

• EUROPE: for Cell-based preparation only - EP 2.6.27

• US:

Expected: USP <72> not approved and published yet

• CHINA: ChP 9406

CoMPENDIAL APPROACH

USP <1225>

Validation of Compendial Procedures

USP <1226>

Verification of Compendial Procedures

When a method is compendial, only the method's suitability with the product is required.

BIOFIRE MYCOPLASMA

Alternative Mycoplasma detection

NAT approach is currently described in pharmacopoeia but still in an alternative status. Several texts are under development to used NAT as compendial method but still not published.

USP <77> Mycoplasma Nucleic Acid Amplification Tests and EP 2.6.7 : onGoing

ALTERNATIVE APPROACH

USP <1223>

EP 5.1.6

JP G4.6.170

The chapters of the Pharmacopoeia dedicated to validation are guidelines and explain how to do.

Same for PDA TR33

Full validation of an alternative method must demonstrate its equivalence (or superiority) to the compendial method.