Pharmaceutical Testing in Pakistan: What Manufacturers Outsource

What gets outsourced, and why

Routine identity, assay and physical testing usually stays in house, because the volume justifies the equipment and release needs a fast turnaround. The outsourcing decision is a fixed cost against a variable one: an instrument costs money whether or not there is work for it.

Accreditation adds a second cost. Under ISO/IEC 17025 a laboratory is accredited for specific methods, so a manufacturer that brings a test in house for two runs a year also takes on its scope assessment and proficiency testing. A test report can only support what its method scope covers.

The published limits behind each test

Know the number before the report arrives. These are the limits the main outsourced tests answer to, from the source documents:

The DEG and EG requirement is not paperwork. The FDA guidance links contaminated syrups to more than 300 deaths, mostly children under 5, in at least seven countries, and notes that in Oct 2022 Indonesian authorities found DEG and EG in a propylene glycol excipient.

Worked examples: turning a limit into a specification

Elemental impurities. ICH Q3D converts a daily limit into a concentration: permitted µg/g = PDE in µg/day ÷ daily intake of the drug product in g/day. For a product taken at 2 g a day, lead at 5 µg/day allows 2.5 µg/g in each component (Option 2a), five times the 0.5 µg/g that Option 1 assumes for a 10 g daily dose.

Nitrosamines. FDA's conversion is ppm = acceptable intake in ng/day ÷ maximum daily dose in mg. For a drug with a maximum daily dose of 320 mg, NDMA at 96 ng/day becomes a limit of 0.3 ppm. Ask the laboratory for its quantitation limit before testing: a method that cannot see 0.3 ppm cannot pass the batch.

Stability. For a 24-month shelf life, ICH Q1A(R2) recommends long-term testing every 3 months in the first year, every 6 months in the second and annually after that, and at least three time points (0, 3 and 6 months) at the accelerated condition of 40 °C/75% RH. On three primary batches that is:

• Long term at 30 °C/65% RH: 7 time points (0, 3, 6, 9, 12, 18, 24 months) × 3 batches = 21 pulls.

• Accelerated at 40 °C/75% RH: 3 time points × 3 batches = 9 pulls.

• Total: 30 full test sets, with chamber space held for two years. That is the capacity a contract laboratory has to commit.

WHO's table of stability conditions (update of Mar 2021) lists Pakistan's confirmed long-term condition as 30 °C/65% RH, so a product registered for Pakistan should be studied there, not at 25 °C/60% RH. Export markets set their own condition; confirm it with each importing regulator before samples go into the chamber.

A contract laboratory tests and reports; it does not release the batch

A contract testing laboratory and a contract manufacturing organisation are often confused, and the confusion leaves a gap in accountability. A contract testing laboratory tests samples the client supplies and reports results. It does not release product and takes no responsibility for the manufacturing process. A contract manufacturing organisation makes the product under the client's licence and carries manufacturing responsibility for it.

So put the appointment in writing: what is tested, by which method, and who releases the batch. In Pakistan the regulator is the Drug Regulatory Authority of Pakistan; international procurement often turns on WHO prequalification and on inspection regimes aligned to PIC/S. Each expects a named party to be accountable for release.

Check a contract laboratory on six points

• Accreditation scope for the method and matrix. "ISO 17025 accredited" is not enough. Accreditation for one assay does not cover another that runs on the same instrument.

• Method transfer records. When a method moves between laboratories, the transfer is documented, not assumed.

• Data integrity controls. Instrument audit trails switched on, controlled access to the chromatography data system, individual logins only.

• Proficiency testing for the relevant methods, with the latest round and its outcome available on request.

• Sample chain of custody from receipt through storage to disposal, with storage conditions recorded.

• Audit rights written into the agreement.

Then ask: which methods on the scope cover the work being sent? A laboratory should answer from its scope document, not from memory.

What the report has to show

For nutraceuticals and herbal products the same logic applies to identity, potency and contaminants: label-claim verification, heavy metals and pesticide residues carry the commercial risk.

Where Tti Labs fits

• ISO/IEC 17025 testing under PNAC LAB-022. Its pharma section lists microbial enumeration and specified organisms (USP <61> and <62>), sterility (USP <71>), endotoxin (USP <85> and <161>), NDMA and NDEA by FDA methods, and DEG and EG in propylene glycol, glycerin and sorbitol to the USP-NF monographs.

• Wider pharmaceutical services for raw materials, APIs, excipients and finished dosage forms: assay and purity, impurities including residual solvents and elemental impurities, stability and shelf-life studies, method development and validation to ICH quality guidelines and pharmacopoeial requirements, extractables and leachables, and container closure integrity.

• Instruments: HPLC with UV/Vis, DAD and MS/MS detection, LC-MS/MS, single and triple quadrupole systems, GC-FID, GC-MS, headspace GC-MS, AAS, ICP-OES, ICP-MS, UV/Vis, FTIR and ELISA kits.

• A US IAC certified microbiology laboratory with ISO Class 5 and Class 7 areas, for sterility, endotoxin (LAL), bioburden, preservative efficacy and environmental monitoring.

• Nutraceutical and herbal testing: vitamins and minerals, fatty acid and nutritional profiles, heavy metals, pesticide residues and herbal extracts.

For any method not named in the LAB-022 pharma section, ask whether the result will be issued under accreditation before sending samples. Tti Labs tests samples and reports results. It does not release batches, act as a contract manufacturer or grant marketing authorisation.

Discuss pharmaceutical testing with Tti Labs or contact the laboratory. UAN 111 786 001. ISO/IEC 17025 accredited through PNAC, LAB-022. US IAC certified microbiology laboratory.

Related guides: Food and Agricultural Export Testing in Pakistan: The Certification Route.