Pharmaceutical-grade active pharmaceutical ingredient (API)
Buying a chemically synthesised API for drug product manufacture · ICH Q7 GMP and traceability back to the original manufacturer, the certificate of analysis, retest dating and reserve samples, ICH Q3A impurity thresholds and ICH Q3C residual solvent classes
An active pharmaceutical ingredient (API), or drug substance, is the substance in a medicine that provides its pharmacological effect; pharmaceutical grade means it is made under API good manufacturing practice and released against a specification fit for use in a drug product. A buyer does not purchase an API as a generic commodity but as a named substance from an identified manufacturing site. Ask three things first: who the original manufacturer is and under which GMP and regulatory filings it supplies, what specification and certificate of analysis will accompany each batch, and which impurity and solvent limits apply at your dose.
Chemically synthesised small-molecule APIs supplied to drug product manufacturers, and the GMP, documentation and impurity requirements set out in ICH Q7, Q3A and Q3C. Biological, peptide and radiopharmaceutical substances, excipients and finished dosage forms are outside this page except where the guidelines compare them.
CNFX editorial research · Sources checked October 11, 2026 · 4 sources
Qualify the manufacturer, the documents and the supply chain
ICH Q7 is the GMP guide for APIs. It applies from the point where an API starting material, a material incorporated as a significant structural fragment of the API, enters the process. It requires a quality unit independent of production that covers both quality assurance and quality control, a formal change control system for changes in raw materials, specifications, methods, facilities, equipment and processing steps, and records kept for at least 1 year after the batch expiry date, or 3 years after complete distribution for APIs with retest dates. [1]
Authentic certificates of analysis should be issued for each batch on request, giving the API name and grade where appropriate, batch number, release date and the expiry or retest date, and listing each test with its acceptance limits and numerical results; certificates are dated and signed. Expiry or retest dates come from stability studies, with a retest date described as standard practice rather than an expiration date, and reserve samples of each batch are kept for one year after expiry or three years after distribution, whichever is longer. [1]
Agents, brokers, traders, distributors, repackers and relabellers are expected to comply with GMP, keep full traceability including the identity and address of the original manufacturer, its batch number and all authentic certificates of analysis, pass quality and regulatory information in both directions, and give the customer the name of the original manufacturer and the batch numbers supplied. Contract manufacturers and laboratories also fall under Q7 and should be evaluated by the contract giver under a written agreement. [1]
Ask for the original manufacturer's name and site address, its GMP inspection or certification history, the regulatory filing to be referenced for your market, the specification and a sample certificate of analysis, the retest or expiry period with stability data, change-notification terms and, for traders, the full traceability documents.
02
Set impurity and residual-solvent limits for your dose
ICH Q3A(R2) covers impurities in new drug substances made by chemical synthesis. For a maximum daily dose of up to 2 g it sets a reporting threshold of 0.05%, an identification threshold of 0.10% or 1.0 mg per day intake, whichever is lower, and a qualification threshold of 0.15% or 1.0 mg per day, whichever is lower; above 2 g per day the thresholds are 0.03%, 0.05% and 0.05%. Higher reporting thresholds need scientific justification, and lower thresholds can be appropriate for unusually toxic impurities. Impurities above the identification threshold should be identified, and those above the qualification threshold qualified by safety data. [2]
ICH Q3C(R8) places residual solvents in three classes: Class 1 solvents to be avoided (benzene 2 ppm, carbon tetrachloride 4 ppm, 1,2-dichloroethane 5 ppm, 1,1-dichloroethene 8 ppm, 1,1,1-trichloroethane 1,500 ppm); Class 2 solvents to be limited, with Option 1 concentration limits calculated as 1,000 × PDE / dose assuming 10 g of product daily; and Class 3 solvents of low toxic potential, where 50 mg per day or less, corresponding to 5,000 ppm or 0.5% under Option 1, is acceptable without justification. If only Class 3 solvents are present, a non-specific test such as loss on drying may be used, and a supplier can state, for example, that only Class 3 solvents are likely to be present and loss on drying is below 0.5%. [3]
Editorial calculation: for a drug dosed at 0.5 g of API per day, the 1.0 mg per day alternative equals 1.0 / 500 = 0.20%, so the 0.10% identification and 0.15% qualification percentages are the lower and govern, matching the guideline's own 0.5 g example. [2]
Nitrosamines are handled separately from the Q3A thresholds. FDA's CDER page, which supports its guidance Control of Nitrosamine Impurities in Human Drugs (Rev. 2, September 2024), explains that nitrosamines form when secondary, tertiary or quaternary amines react with nitrous acid (nitrite salts under acidic conditions), and separates small-molecule nitrosamines from nitrosamine drug substance-related impurities (NDSRIs) that share structure with the API. Its Table 2 gives compound-specific recommended acceptable intake (AI) limits, for example 96 ng/day for NDMA, 26.5 ng/day for NDEA, 1,300 ng/day for N-nitroso-piperazine (source: ciprofloxacin) and 100 ng/day for N-nitroso-duloxetine; Table 1 assigns limits of 26.5, 100, 400 or 1,500 ng/day from the predicted Carcinogenic Potency Categorization Approach (CPCA). FDA states the limits are recommendations and that an alternative approach can be used if it satisfies the applicable statutes and regulations. [4]
Editorial calculation: for an API taken at 1 g per day, 96 ng/day of NDMA is 96 ng ÷ 1 g = 0.096 ppm (0.0000096%), about 5,000 times below the 0.05% Q3A reporting threshold, so ask the supplier for a nitrosamine risk assessment and a method sensitive enough for the AI limit at your maximum daily dose. [4][2]
Give the supplier the maximum daily dose and route, the pharmacopoeial monograph or in-house specification, the solvents used in the last steps as you understand them, and any polymorph, particle size or water content needed by your formulation.
Fill the specification fields with values for your substance
The table explains each field, gives values where a reviewed guideline states them, and says what to obtain from the supplier. Limits for a named API come from its monograph or registered specification.
Explore company information and manufacturing capabilities, then discuss the scope of your project with a relevant supplier.
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Compiled and source-reviewed by the CNFX editorial team.
Published product pages show what a company offers, not GMP status or regulatory standing. Confirm the original manufacturer, site, GMP inspections and filings for your substance and market. How we source and review
· Page last updated 13 October 2026
Buyer questions
What GMP standard applies to API manufacture?
ICH Q7, from the introduction of the API starting material onward. [1]
Must a trader disclose the original API manufacturer?
Q7 says the supplier should give the customer the original manufacturer's name and batch numbers. [1]
What impurity thresholds apply to a new drug substance?
For up to 2 g/day: report above 0.05%, identify above 0.10%, qualify above 0.15% (or 1.0 mg/day if lower). [2]
What is the limit for Class 3 residual solvents?
50 mg per day or less, 5,000 ppm or 0.5% under Option 1, without justification. [3]
What nitrosamine limits does FDA recommend for APIs?
FDA's CDER page lists recommended acceptable intakes such as 96 ng/day for NDMA and 26.5 ng/day for NDEA, and CPCA-based limits of 26.5 to 1,500 ng/day for other nitrosamines. [4]
Sources and what still needs a direct check
Sources checked 2026-10-11. ICH guidelines set the framework, and FDA's nitrosamine page gives US recommended intake limits for one impurity class; limits for a named API come from its monograph and registered specification. Verify every value with the manufacturer and your regulatory team.
