1. Regulatory background – why this notification came
- Multiple child-death incidents (Gambia, Uzbekistan, later in Indian states like MP & Rajasthan) were traced to cough syrups heavily contaminated with DEG and EG.Indian Journal of Medical Ethics+1
- Investigations showed industrial-grade solvents and adulterated glycerin/propylene glycol entering oral liquid formulations.Reuters+1
- WHO issued a testing protocol for DEG/EG in liquid oral dosage forms and recommended that each should be ≤ 0.10% (m/m) individually.WHO
India has now translated this into binding pharmacopoeial and regulatory requirements.
2. What the Indian Pharmacopoeia amendment says (Oral Liquids)
Indian Pharmacopoeia (IP) 2022 – Amendment List 09 (10 Oct 2025):
- Scope
- The amendment adds a mandatory DEG & EG test to the General Monograph “Oral Liquids”.
- It applies to all oral liquid formulations: syrups, suspensions, solutions, elixirs, drops, paediatric syrups, etc.LinkedIn+1
- Placement in monograph
- The test is to be inserted before “Uniformity of Content” in the Oral Liquids monograph (IP p. 1335).LinkedIn
- Test method
- Gas Chromatography as per IP General Chapter 2.4.13 – Gas Chromatography is the official method.LinkedIn+1
- Limit
- “Not more than 0.10% of each DEG and EG in the final product” (m/m), harmonised with WHO’s limit for oral liquids.LinkedIn+1
- Responsibility
- Laboratories and manufacturers must update their monographs / STPs, methods and records to incorporate this test and be ready to show evidence during audits and inspections.LinkedIn
3. DCGI / CDSCO directions beyond IP
Following the MP child-death incident:
- DCGI has made DEG/EG testing mandatory in both:
- Raw materials (high-risk excipients and solvents) and
- Finished pharmaceutical products (all oral liquids).The Times of India
Earlier, most companies were only testing selected raw materials; now the finished product test is explicitly mandatory under IP, and DCGI has ordered stricter implementation across India.
State drug controls are echoing this:
- Example: Telangana DCA Circular (13-10-2025) to all liquid-oral manufacturers mandates:
- Procurement of glycerin, propylene glycol, sorbitol solution, etc. directly from manufacturers,
- Use of only pharmacopoeial-grade excipients,
- Mandatory DEG/EG testing of these raw materials before use,
- With a limit of NMT 0.10% as per respective pharmacopoeial monographs.dca.telangana.gov.in+1
4. What this means for you (manufacturer / QA / QC)
Think in three layers: raw materials → in-process → finished product.
A. Raw materials & suppliers
- Identify “high-risk” excipients / solvents used in your oral liquids, e.g.:
- Glycerin
- Propylene Glycol
- Sorbitol Solution / Maltitol Solution / Hydrogenated starch hydrolysate
- Polyethylene glycol (PEG) with MW < 1000
- Ethanol (ethyl alcohol) and other solvent-type excipients
These appear repeatedly in WHO, FDA and CDSCO communications as high-risk for DEG/EG contamination.Redica Systems+3WHO+3U.S. Food and Drug Administration+3
- Supplier qualification & approval
- Procure directly from original manufacturers where possible; avoid unlicensed traders.dca.telangana.gov.in+1
- Ensure pharmacopoeial-grade material and clear specification: “DEG & EG NMT 0.10% each” (or tighter, if you set an internal alert limit).
- Require COAs with DEG/EG results, but do not rely only on supplier COA – do periodic or every-batch confirmatory testing (risk-based).LinkedIn+1
- Incoming QC testing
- Include DEG/EG in STPs for all high-risk excipients using GC (as per IP / WHO / FDA guidance).WHO+2U.S. Food and Drug Administration+2
- Clearly define sampling plan, acceptance criteria (≤0.10%), and actions for OOS / suspected fraud.
B. In-process controls
- Manufacturing controls
- Ensure positive identification of drums and tanks to avoid any chance of mixing industrial-grade solvents with pharma-grade materials (e.g., clear labelling, barcode systems).
- Implement line clearance and proper cleaning of mixing vessels and transfer lines to prevent cross-contamination of DEG/EG from any previous batch or non-pharma use.
- Risk assessment
- Update your Quality Risk Management (QRM) documentation (ICH Q9) to explicitly include DEG/EG contamination risk for all oral liquids.
- Identify critical control points (receipt of excipient, bulk solution make-up, filtration, storage, filling).
C. Finished product testing & release
- Mandatory test in specifications
- For each oral liquid, revise finished product specifications to add: “Test for Diethylene glycol and Ethylene glycol (GC, IP 2.4.13) – each NMT 0.10%.”LinkedIn+2The Times of India+2
- Analytical method
- Adopt / validate a GC-FID method aligned to IP 2.4.13 or WHO’s confirmatory GC procedure (sample prep, IS, calibration range around 0.10%).WHO+1
- Ensure LOD/LOQ are below 0.10%, so the method can reliably detect and quantify at the regulatory limit.
- Batch release
- No batch of oral liquid (for domestic or export) should be released without a compliant DEG/EG result recorded in the COA and Batch Manufacturing Record.CDSCO+2ScienceDirect+2
- For contract testing labs, keep test requisition forms, raw data, chromatograms and calculation sheets on file for audits.
5. Documentation, training & change control
- SOP / STP revisions
- Update SOPs for vendor qualification, raw material testing, finished product testing, OOS handling and product recall to incorporate DEG/EG controls.TaxTMI
- Change control
- Route all updates (methods, specs, labels if needed) through the formal change control system, with impact assessment on stability, validation and regulatory filings.
- Training
- Train Production, QC, QA & Warehouse staff on:
- What DEG/EG are and why they’re dangerous,
- New sampling and testing requirements,
- How to read COAs and spot red flags,
- How to act on OOS or suspect materials.www.pharmabiz.com+1
- Train Production, QC, QA & Warehouse staff on:
6. Quick compliance checklist (for your site)
You can almost use this as a one-page poster or internal audit list:
- All oral liquids have DEG & EG test in finished product specs (GC, NMT 0.10% each).
- All relevant excipients (glycerin, PG, sorbitol, maltitol, PEG, etc.) are on a high-risk excipient list with DEG/EG limits.
- Supplier qualification covers DEG/EG risk; materials are procured from approved manufacturers only.
- Incoming QC includes DEG/EG testing for high-risk excipients, with defined sampling plan and OOS SOP.
- GC method for DEG/EG is validated / verified and in routine use; analysts are trained.
- Batch records and COAs for oral liquids clearly show “DEG/EG – Complies” with actual values or “< LOQ” reported.
- QRM, change control and training records updated to reflect the new regulatory requirements.
SOP Title: Control of Diethylene Glycol (DEG) and Ethylene Glycol (EG) in Oral Liquid Formulations
SOP No.:
Effective Date:
Revision No.:
Supersedes:
Department: QA / QC / Production / Warehouse
Prepared by / Reviewed by / Approved by:
1. Purpose
- To define the procedure for preventing, detecting and controlling contamination of oral liquid formulations with DEG and EG.
- To ensure compliance with pharmacopoeial requirements (e.g., IP “Oral Liquids” monograph) and regulatory directives for DEG/EG control in:
- High-risk excipients and solvents
- Bulk solutions
- Finished oral liquid products
2. Scope
- Applicable to all oral liquid dosage forms manufactured / tested at [Company / Site Name], including but not limited to:
- Syrups, solutions, elixirs, drops, suspensions, paediatric oral liquids, etc.
- Covers:
- Procurement and receipt of high-risk excipients and solvents
- Sampling and testing of raw materials for DEG/EG
- In-process controls related to DEG/EG
- Finished product testing for DEG/EG
- Handling of non-conformities (OOS / suspect contamination)
3. References
- Indian Pharmacopoeia, current edition – General Monograph: Oral Liquids (DEG/EG test & limits)
- IP General Chapter “Gas Chromatography” (e.g., 2.4.13)
- WHO / national regulatory guidelines, alerts or circulars regarding DEG/EG contamination in oral liquids
- ICH Q7, Q9, Q10 (as applicable)
- Internal SOPs:
- Vendor Qualification
- Change Control
- OOS / OOT Handling
- Product Recall
- Deviation Management
4. Definitions
- DEG – Diethylene Glycol, a toxic glycol potentially contaminating excipients/solvents.
- EG – Ethylene Glycol, a toxic glycol potentially contaminating excipients/solvents.
- High-risk excipients / solvents – Excipients or solvents with known risk of DEG/EG contamination, e.g. glycerin, propylene glycol, sorbitol solution, maltitol solution, PEG (low MW), ethanol, etc.
- NMT – Not More Than.
- LOQ – Limit of Quantitation of the analytical method.
5. Responsibilities
Quality Assurance (QA)
- Ensure implementation of this SOP.
- Approve DEG/EG specifications, STPs and any revisions.
- Approve and close deviations/OOS related to DEG/EG.
- Ensure change control for any updates to methods, suppliers, or specifications.
Quality Control (QC)
- Prepare and maintain analytical methods/STPs for DEG/EG determination using GC.
- Perform incoming raw material, in-process (if applicable), and finished product testing for DEG/EG.
- Maintain raw data, chromatograms, calculations and ensure timely reporting of OOS results.
Production
- Ensure only released and approved raw materials are used in manufacturing.
- Maintain line clearance, equipment cleaning and identification to prevent cross-contamination.
- Record batch details for traceability of excipients/solvents.
Warehouse / Stores
- Ensure procurement only from approved vendors.
- Ensure proper segregation, labelling and storage of high-risk excipients.
- Prevent mix-up of industrial-grade and pharma-grade materials.
Regulatory Affairs (if applicable)
- Ensure regulatory filings (if required) reflect inclusion of DEG/EG tests and limits.
6. Procedure
6.1 Identification of High-Risk Excipients and Solvents
6.1.1 QA, with QC and Production, shall maintain a “High-Risk Excipients & Solvents List” containing at minimum:
- Glycerin
- Propylene Glycol
- Sorbitol solution / other polyol solutions
- PEGs (as applicable)
- Ethanol (ethyl alcohol) and other solvents used in oral liquids
6.1.2 For each excipient/solvent on the list, the material specification shall include:
- Test: DEG & EG
- Limit: NMT 0.10% of each (w/w) or tighter, as per site policy
6.1.3 The list shall be periodically reviewed (e.g., annually or after any new regulatory alert) and updated via change control.
6.2 Vendor Qualification and Material Procurement
6.2.1 Only approved vendors/manufacturers shall be used for high-risk excipients.
6.2.2 Vendor qualification shall ensure:
- Supply of pharmacopoeial-grade material with defined DEG/EG controls.
- Evidence of testing for DEG/EG at vendor’s site (method summary, typical COA).
6.2.3 Purchase orders for high-risk excipients shall specify:
- “Material must comply with DEG & EG NMT 0.10% each.”
6.2.4 Warehouse shall verify that each lot received has:
- Valid COA including DEG/EG results.
- Matching manufacturer, batch number, and grade as per PO.
6.2.5 Any discrepancy shall be handled through material discrepancy / deviation and material shall be kept quarantined.
6.3 Receipt, Sampling and Testing of High-Risk Excipients
6.3.1 On receipt, high-risk excipients shall be quarantined until approved by QC.
6.3.2 Sampling shall be performed as per SOP for Material Sampling, ensuring:
- Use of clean and dedicated sampling tools.
- Proper labelling of samples for DEG/EG testing.
6.3.3 QC shall perform DEG/EG testing as per approved GC method (see 6.6).
6.3.4 Acceptance criteria:
- DEG: NMT 0.10%
- EG: NMT 0.10%
6.3.5 If results fail or are suspect:
- Treat as OOS; follow OOS SOP.
- Place entire lot under rejection / investigation until disposition.
6.3.6 Only lots meeting requirements shall be released by QA for production use.
6.4 In-Process Controls (IPC)
6.4.1 Production shall verify that only released high-risk excipient lots are used in each batch.
6.4.2 Batch Manufacturing Record (BMR) shall document:
- Material name, grade, batch/lot number, quantity used.
6.4.3 Equipment and transfer lines shall be cleaned and cleared as per SOP to avoid cross-contamination with any non-pharma or other DEG/EG-containing substances.
6.4.4 Where justified by risk assessment, QC may perform periodic DEG/EG checks in bulk solution before filling (e.g., for paediatric syrups, high-risk markets).
6.5 Finished Product Specifications and Testing
6.5.1 All oral liquid finished products shall have a specific test for DEG & EG included in the product specification.
6.5.2 QC shall test each commercial batch (and PPQ/stability batches as applicable) using the approved GC method.
6.5.3 Acceptance criteria (example):
- DEG: NMT 0.10% of the formulation
- EG: NMT 0.10% of the formulation
6.5.4 Results shall be recorded in test reports and COAs, indicating:
- Actual values or “< LOQ” (specify LOQ).
6.5.5 Any failure to comply shall be handled under OOS SOP, and QA shall evaluate batch rejection and recall implications where needed.
6.6 Analytical Method (GC) for DEG/EG
(Outline only – full STP to be separate attachment.)
6.6.1 Method Principle
- Determination of DEG and EG using Gas Chromatography (GC) with suitable detector (e.g. FID).
6.6.2 System Suitability & Calibration
- Standard solutions prepared at relevant concentration range around the limit of 0.10%.
- System suitability parameters (e.g., resolution between DEG and EG peaks, %RSD, etc.).
6.6.3 Sample Preparation
- Defined sample dilution, internal standard (if used), extraction conditions.
6.6.4 Validation / Verification
- Method validated/verified for specificity, linearity, accuracy, precision, LOQ, robustness as per internal validation SOP.
6.6.5 Documentation
- Chromatograms, integration reports, calculations and results shall be retained and traceable to the material/batch tested.
6.7 Handling of Out-of-Specification (OOS) / Deviations
6.7.1 Any OOS result or atypical chromatogram for DEG/EG shall be investigated as per OOS SOP.
6.7.2 Investigation shall include, where applicable:
- Check of sample prep, standards, system suitability.
- Resampling and retesting where justified.
- Evaluation of other batches / lots of same excipient or product.
- Assessment of potential patient safety impact.
6.7.3 QA shall decide final batch/material disposition (reject, rework if scientifically justified, or other).
6.7.4 For confirmed contamination or critical trend, QA shall coordinate:
- Regulatory notification (if applicable).
- Field alert / recall, as per recall SOP.
6.8 Training
6.8.1 QA shall ensure all relevant personnel (QC, Production, Warehouse) are trained on:
- Hazards of DEG/EG.
- This SOP and related STPs.
- Identification and handling of high-risk excipients.
6.8.2 Training shall be documented; effectiveness checks (e.g. quizzes) may be conducted.
6.9 Documentation and Records
6.9.1 The following records shall be maintained with defined retention periods:
- Approved vendor list and qualifications for high-risk excipients.
- Material specifications, test methods and validation reports.
- Sampling records and test reports for raw materials.
- Batch manufacturing records and batch packaging records.
- Finished product test reports and COAs showing DEG/EG results.
- OOS/deviation/recall records related to DEG/EG.
- Training records.
6.10 Change Control & Periodic Review
6.10.1 Any change impacting DEG/EG control (new supplier, new excipient, method change, new product, etc.) shall be handled via formal change control.
6.10.2 This SOP and associated methods shall be periodically reviewed (e.g., every 2 years) or earlier in case of:
- New regulatory requirements, alerts or pharmacopoeial changes.
- Internal audit / external inspection findings.
7. Annexures (Examples)
- Annexure I – High-Risk Excipients & Solvents List (with product mapping)
- Annexure II – Template: DEG/EG Raw Material Test Report
- Annexure III – Template: DEG/EG Finished Product Test Summary on COA
- Annexure IV – Flowchart: DEG/EG Control from Vendor to Finished Product
- Annexure V – Training Attendance Sheet