Pharmaceutical Raw Material Testing — Ph. Eur. / USP Monograph

What Is Raw Material Testing?

Pharmaceutical raw material testing examines the active pharmaceutical ingredient (API) and excipients to be used in manufacture against every heading defined in the relevant pharmacopoeia monograph. The monograph specifies headings such as identity, assay, impurity profile, solubility, loss on drying, sulphated ash, heavy metals and microbiological quality, and the acceptance criterion for each.

Purpose of Raw Material Testing

The purpose is to verify the raw material entering manufacture is the declared substance and meets pharmacopoeial quality. Good manufacturing practice makes this verification mandatory at raw material acceptance.

Which Products Is Raw Material Testing Applied To?

Active pharmaceutical ingredients (API)
Excipients
Packaging and closure materials
Water and solvents
Herbal drugs and extracts

In Which Sectors Is Raw Material Testing Used?

PharmaceuticalsBiotechnologyChemistry

Standards Related to Raw Material Testing

Ph. Eur. relevant substance monographs and general chapters
USP-NF relevant monographs
ICH Q6A (specifications: new drug substances and products)
ICH Q3D (elemental impurities)
ICH Q3C (residual solvents)

Raw Material Testing Conditions

Scope: All headings in the monograph; partial analysis does not demonstrate full compliance
Reference standard: Pharmacopoeia reference standards are used
Sampling: Representative sampling from containers; per GMP rules

Equipment for Raw Material Testing

HPLC and GC systems
FTIR and UV/Vis spectrophotometer
ICP-MS (elemental impurities)
Karl Fischer titrator and oven
Microbiology laboratory

Sample Requirements for Raw Material Testing

Specimen with its certificate of analysis and monograph reference
Sufficient quantity; a separate specimen is needed for every test in the monograph
Batch number and manufacturer information must be provided
The specimen must be sent in its original packaging and per its storage condition

Duration of Raw Material Testing

Duration depends on the number of tests in the monograph. Chemical and instrumental tests take several working days, while microbiological headings require their own incubation times.

Raw Material Testing Procedure

1The relevant pharmacopoeia monograph and edition are determined.
2Sampling is carried out per GMP rules.
3Identity tests are applied.
4Assay and impurity analyses are carried out.
5Physical and chemical property tests are performed.
6Results are compared against the criteria in the monograph.

Raw Material Testing Acceptance Criteria

The acceptance criterion is not given on this page: for every active substance and every product, the limit comes from the relevant pharmacopoeia monograph or the approved specification in the marketing authorisation dossier. The pharmacopoeia's general chapter defines the method; the monograph sets the limit.

Evaluation of Results

The monograph is a whole: passing one heading does not cover the others, and a "complies with the pharmacopoeia" claim cannot be made from partial analysis. The report also states which pharmacopoeia and edition were applied; method and criteria can change between editions.

Raw Material Testing Report

Specimen identification, batch and manufacturer information
Pharmacopoeia and edition applied
Method, result and criterion for each heading
Reference standards used
Overall compliance assessment

Accreditation

EUROLAB holds internationally recognised accreditation obtained from accreditation bodies party to the IAF and ILAC multilateral recognition arrangements, under ISO/IEC 17025 for laboratory testing, ISO/IEC 17020 for inspection and surveillance, and ISO/IEC 17021-1 and ISO/IEC 17065 for system and product certification. This chain ensures the reports and certificates issued are accepted worldwide.

Whether this test can be offered within accredited scope depends on your product and the standard applied; since accreditation is method-based, the scope is confirmed in writing at the quotation stage.

Scope and authorisations

Related Regulations

2001/83/EC Directive on Medicinal Products for Human Use
(EU) 2017/1572 and the GMP Guide (EudraLex Volume 4)

Pharmaceutical Analysis — What Does This Testing Field Cover?

The section below describes the field that the Raw Material Testing test belongs to; the conditions and acceptance criteria of this particular test are given in the sections above. The scope specific to your product is confirmed in writing at the quotation stage.

Pharmaceutical analysis determines the identity, purity, quantity and behaviour of an active substance and of the finished product. What sets this family apart is that the methods are largely defined in PHARMACOPOEIAS: the European Pharmacopoeia (Ph. Eur.) and the United States Pharmacopeia (USP) give both the method and the acceptance framework together.

The binding nature of the pharmacopoeial method shapes how the field works. In other sectors a laboratory can choose a suitable method, whereas here the method in the monograph governs; if an alternative method is to be used, its equivalence must be demonstrated. This is what makes results comparable worldwide.

Analyses are carried out in several groups. Identity and assay (HPLC, UV, titration) show what the product is and how much active substance it contains. The impurity profile and residual solvents look for unwanted compounds arising from the manufacturing process. Elemental impurities address metals originating from catalysts and equipment. Dissolution and disintegration behaviour is the most important in vitro indicator of how the drug will be released in the body.

The DISSOLUTION TEST is one of the most critical measurements in the field. It is not enough for a tablet to contain the right amount of active substance; that substance must dissolve at a suitable rate. The dissolution profile is used to assess the effect of formulation changes on bioavailability and holds a central place in generic drug licensing.

METHOD VALIDATION is a mandatory step in this family. If a pharmacopoeial method is used, it is verified that the method works properly under that laboratory's conditions. If an in-house method has been developed, it is validated against parameters such as linearity, precision, accuracy, specificity, limits of detection and quantification, and robustness. A result produced with an unvalidated method cannot be used in a licence dossier.

Stability studies determine shelf life and are the longest-running work in the field. The product is held under defined temperature and humidity conditions, analysed at set intervals, and the results become the basis of the shelf life and storage condition claims. Accelerated conditions give preliminary information but real-time data is what counts.

The microbiological side is a separate body of work: microbial enumeration, testing for specified microorganisms, sterility testing for sterile products and the bacterial endotoxin test. For sterile products, packaging integrity and sterilisation validation also come into play.

Data integrity has moved to the centre of inspections in recent years. It is not enough for the result to be correct; the raw data must be traceable, unalterable and auditable. Validation of electronic record systems has therefore become an inseparable part of analysis.

Method groups in this field

Identity and assay
HPLC, UPLC, UV-Vis spectrophotometry, titration, identity confirmation by FTIR.
Impurities and residues
Related impurities, degradation products, residual solvents (GC headspace), nitrosamine screening.
Elemental impurities
Determination of elemental impurities by ICP-MS and ICP-OES and the associated risk assessment.
Physicochemical
Dissolution and disintegration, hardness, friability, uniformity of dosage units, water content (Karl Fischer), particle size.
Microbiological
Microbial enumeration, specified microorganisms, sterility, bacterial endotoxin, preservative efficacy.
Stability
Real-time and accelerated stability studies; photostability and in-use stability.

Commonly confused in this field

The pharmacopoeial method is binding; an alternative method may be used only by demonstrating its equivalence.
A result produced without method validation cannot be used in a licence dossier.
Accelerated stability does not replace real-time data; shelf life is supported by real-time results.
The dissolution profile is sensitive to apparatus type, agitation rate and medium; the conditions must be complete in the report.
A shortcoming in data integrity produces a non-conformity in an inspection even when the result is correct.
A change of formulation or supplier requires analytical comparison and, where necessary, a new stability study.

Which decisions these results support

The licence dossier and batch release
Determining shelf life and storage conditions
Method transfer and method validation
Incoming raw material acceptance control from suppliers
Assessing the effect of a formulation change on bioequivalence

Related Tests

Frequently Asked Questions About Raw Material Testing

Is the supplier's certificate of analysis sufficient?

GMP requires supplier qualification and periodic verification before a supplier's certificate can be relied upon. Identity testing must still be performed by the manufacturer on every batch; a certificate does not substitute for it.

Is there a difference between Ph. Eur. and USP?

Criteria and methods can differ for the same substance. Which pharmacopoeia's compliance is required is defined in the marketing authorisation dossier; the two pharmacopoeias do not automatically substitute for each other.