Diethylene Glycol (DEG) Contamination in Pharmaceuticals

05/10/2025 · by · in neuropsychiatry · Leave a comment

History of Diethylene Glycol (DEG) Contamination in Pharmaceuticals

Diethylene glycol (DEG) is a toxic industrial solvent used in products like antifreeze and brake fluids. Its accidental or fraudulent use as a substitute for safer solvents like glycerin or propylene glycol in pharmaceutical products, particularly cough syrups and liquid medications, has led to multiple mass poisoning incidents globally over decades. Below is a detailed history of significant DEG contamination cases, focusing on key incidents, their impacts, and regulatory responses.

Notable DEG Contamination Incidents

  1. 1937: United States – Elixir Sulfanilamide Tragedy
  • Details: The first major recorded DEG poisoning occurred when S.E. Massengill Company used DEG as a solvent in Elixir Sulfanilamide, a liquid antibiotic. The drug was marketed without toxicity testing.
  • Impact: Over 100 deaths, mostly children, due to kidney failure. The tragedy exposed the lack of pre-market drug safety regulations in the U.S.
  • Outcome: Prompted the passage of the 1938 Federal Food, Drug, and Cosmetic Act, mandating safety testing for drugs before market release and establishing the U.S. Food and Drug Administration (FDA) as a regulatory body.
  1. 1969: South Africa
  • Details: DEG was used in a sedative syrup, leading to the deaths of seven children from renal failure.
  • Impact: Highlighted the need for stricter global pharmaceutical standards, though specific regulatory changes were limited at the time.
  1. 1986: India – Mumbai
  • Details: Glycerin contaminated with DEG was used in cough syrups at J.J. Hospital, Mumbai, causing acute renal failure in 14 patients.
  • Impact: Exposed weaknesses in India’s drug supply chain and quality control, but systemic reforms were slow to follow.
  1. 1990: Nigeria
  • Details: Paracetamol syrup contaminated with DEG led to the deaths of 47 children.
  • Impact: Raised alarms about substandard drug manufacturing in developing nations. Nigeria began strengthening its drug regulatory framework, though enforcement remained inconsistent.
  1. 1990-1992: Bangladesh
  • Details: Paracetamol syrups laced with DEG caused over 200 child deaths across multiple incidents.
  • Impact: Led to temporary bans on liquid paracetamol and calls for improved testing. However, weak enforcement allowed further incidents.
  1. 1995-1996: Haiti
  • Details: DEG-contaminated paracetamol and cough syrups, sourced from a Chinese supplier via European intermediaries, killed 88 children.
  • Impact: The World Health Organization (WHO) issued warnings about DEG risks. The incident exposed vulnerabilities in global pharmaceutical supply chains, particularly for low-cost generics.
  1. 1998: India – Gurgaon
  • Details: Cough syrup contaminated with DEG caused the deaths of 33 children in Haryana.
  • Impact: Sparked public outrage and led to calls for stricter enforcement of India’s Drugs and Cosmetics Act. However, regulatory gaps persisted.
  1. 2006: Panama
  • Details: Cough syrup imported from China, mislabeled as glycerin but containing DEG, killed over 100 people, including children and adults.
  • Impact: Led to international investigations revealing fraudulent supply chains. Panama banned Chinese pharmaceutical imports, and the FDA issued import alerts. The WHO intensified efforts to standardize global excipient testing.
  1. 2008-2009: Nigeria
  • Details: DEG-contaminated teething syrup (My Pikin) killed 84 children.
  • Impact: Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) cracked down on substandard drugs, prosecuting manufacturers and tightening import regulations.
  1. 2022-2023: Gambia, Uzbekistan, and Indonesia
    • Details:
    • Gambia (2022): Four Indian-manufactured cough syrups (by Maiden Pharmaceuticals) linked to 70 child deaths due to DEG and ethylene glycol (EG) contamination. The syrups were exported to Gambia via intermediaries.
    • Uzbekistan (2022): Another Indian company, Marion Biotech, supplied DEG-contaminated syrups, killing 18 children.
    • Indonesia (2022-2023): Over 200 child deaths were linked to DEG and EG in locally produced syrups, though some raw materials were imported.
    • Impact:
    • WHO issued global alerts, urging stricter testing for DEG and EG in paediatric medicines.
    • India suspended production at implicated firms and mandated propylene glycol testing for export-bound cough syrups from April 2023.
    • Indonesia banned liquid medicines temporarily and later introduced stricter pharmacopoeia standards.
    • The incidents damaged India’s reputation as a global pharmaceutical supplier, prompting calls for centralized drug regulation.
  2. 2025: India – Madhya Pradesh Cough Syrup Scandal
    • Details: Coldrif syrup, manufactured by Sresan Pharmaceuticals in Tamil Nadu, contained up to 48.6% DEG, causing the deaths of at least 11 children (some reports cite 14) in Madhya Pradesh and additional deaths in Rajasthan. The syrup was prescribed by Dr. Praveen Soni, a suspended government paediatrician.
    • Impact: Triggered immediate bans on Coldrif in multiple states, arrests of the manufacturer’s directors, and a nationwide review of cough syrup safety. The Union Health Ministry ordered risk-based inspections, and public outrage has fueled demands for stricter penalties and regulatory reform.
    • Current Status (October 5, 2025): Investigations are ongoing, with potential for new national guidelines on paediatric drug safety.

Common Patterns and Causes

  • Fraudulent Substitution: DEG is cheaper than glycerin or propylene glycol, leading unscrupulous suppliers to use it as a cost-cutting measure. Mislabeling in supply chains often obscures its presence.
  • Weak Regulation: Many incidents occurred in countries with underdeveloped or poorly enforced drug safety standards, particularly for excipients (inactive ingredients).
  • Global Supply Chains: Contaminated raw materials, often sourced from countries like China or India, reach multiple markets, amplifying risks.
  • Target Population: Children are disproportionately affected due to their lower body weight and higher susceptibility to DEG’s toxic effects, which include metabolic acidosis, acute kidney failure, and multi-organ failure.

Regulatory and Industry Responses

  • United States: Post-1937, the FDA implemented rigorous pre-market testing and Good Manufacturing Practices (GMP). DEG testing is now standard for liquid formulations.
  • WHO Guidelines: Since the 1990s, WHO has issued guidelines for testing excipients like glycerin and propylene glycol for DEG contamination. After the 2022 Gambia incident, WHO emphasized mandatory testing for exports.
  • India:
  • The Drugs and Cosmetics Act of 1940 (amended multiple times) governs drug safety, but enforcement has been inconsistent, especially for domestic markets.
  • Post-2022, India mandated DEG/EG testing for cough syrup exports and proposed centralized regulation under the Central Drugs Standard Control Organisation (CDSCO).
  • The 2025 Madhya Pradesh incident has renewed calls for mandatory batch testing and stricter penalties for manufacturers.
  • Global Standards: The International Council for Harmonisation (ICH) and pharmacopoeias (e.g., USP, Indian Pharmacopoeia) now include specific tests for DEG in glycerin-based products. However, compliance varies in low-resource settings.

Ongoing Challenges

  • Supply Chain Oversight: Tracing raw materials across global suppliers remains difficult, especially for small-scale manufacturers.
  • Regulatory Gaps: In countries like India, decentralized regulation (state-level drug controllers) leads to inconsistent enforcement. Domestic markets often face less scrutiny than exports.
  • Economic Pressures: Cost-cutting by manufacturers and suppliers continues to drive DEG substitution.
  • Public Awareness: Lack of awareness among healthcare providers and consumers about DEG risks delays identification of poisoning cases.

Recent Developments (2025 Context)

The 2025 Madhya Pradesh incident underscores persistent issues in India’s pharmaceutical sector. Despite reforms post-2022, the presence of DEG in Coldrif syrup indicates lapses in batch testing and supply chain verification. The Indian government’s response, including risk-based inspections and a proposed national video conference on cough syrup safety, signals intent to address these gaps. However, systemic issues like underfunded regulatory agencies and private practice by government doctors (as seen with Dr. Soni) remain unresolved.

Regulatory Reforms Post-2022 Gambia Cough Syrup Incident

The 2022 Gambia cough syrup incident, where 70 children died due to diethylene glycol (DEG) and ethylene glycol (EG) contamination in four cough syrups manufactured by Maiden Pharmaceuticals in India, exposed significant gaps in pharmaceutical regulation, particularly for exports. The tragedy, combined with similar incidents in Uzbekistan and Indonesia, prompted India and global bodies to introduce reforms aimed at preventing future contamination. Below is a detailed overview of the regulatory reforms implemented post-2022, focusing on India’s response and international efforts.

Reforms in India

  1. Mandatory DEG/EG Testing for Cough Syrup Exports (April 2023)
  • Details: The Central Drugs Standard Control Organisation (CDSCO) mandated that all cough syrups intended for export must be tested for DEG and EG content at government-approved laboratories (e.g., National Institute of Biologicals or regional drug testing labs) before shipment. Certificates of Analysis (CoA) must accompany export consignments.
  • Impact: Ensured that exported syrups meet pharmacopoeia standards (e.g., Indian Pharmacopoeia, USP) for excipient safety, reducing the risk of contaminated products reaching international markets.
  • Scope: Applied to all manufacturers, including small and medium enterprises, which were previously less scrutinized.
  1. Enhanced Good Manufacturing Practices (GMP) Enforcement
  • Details: In 2023, the CDSCO revised Schedule M of the Drugs and Cosmetics Act, 1940, to strengthen GMP requirements. Key changes included:
    • Mandatory quality management systems for raw materials, especially excipients like glycerin and propylene glycol.
    • Stricter audits of manufacturing facilities, with a focus on supply chain traceability.
    • Requirements for manufacturers to maintain records of raw material sourcing and conduct in-house DEG/EG testing.
  • Impact: Aimed to address substandard manufacturing practices, particularly in smaller firms. By mid-2023, over 200 drug manufacturing units were inspected, with 25% found non-compliant and issued show-cause notices or licenses suspended.
  • Challenges: Implementation was uneven due to resource constraints and state-level variations in enforcement.
  1. Risk-Based Inspections
  • Details: The CDSCO introduced a risk-based inspection framework in 2023, prioritizing manufacturers of liquid formulations (e.g., cough syrups) and those with prior compliance issues. Joint inspections by central and state drug controllers were mandated for high-risk facilities.
  • Impact: Identified non-compliant manufacturers, such as Maiden Pharmaceuticals and Marion Biotech (implicated in Uzbekistan). Several firms were shut down or had licenses revoked.
  • Context for 2025: The Madhya Pradesh Coldrif scandal (October 2025) led to a renewed push for risk-based inspections, with the Union Health Ministry ordering nationwide checks on cough syrup manufacturers.
  1. Proposed Centralized Drug Regulation
  • Details: Post-Gambia, the Indian government proposed amending the Drugs and Cosmetics Act to centralize drug regulation under the CDSCO, reducing reliance on state-level drug controllers. A draft bill was discussed in 2023 to empower the CDSCO to oversee licensing and quality control nationwide.
  • Impact: Aimed to address inconsistencies in state-level enforcement, which allowed substandard drugs to enter the market. However, the bill faced resistance from states and was still under review as of October 2025.
  • Relevance to 2025: The Coldrif incident highlighted ongoing issues with state-level oversight, as Sresan Pharmaceuticals operated under Tamil Nadu’s drug controller, reigniting calls for centralization.
  1. Strengthened Supply Chain Oversight
  • Details: The CDSCO issued guidelines in 2023 requiring manufacturers to verify the quality of raw materials (e.g., glycerin, propylene glycol) through supplier audits and third-party testing. Excipient suppliers were required to provide certificates confirming the absence of DEG/EG.
  • Impact: Reduced the risk of contaminated raw materials entering the supply chain, though enforcement remained challenging for small-scale suppliers.
  • 2025 Context: Investigations into Sresan Pharmaceuticals revealed lapses in raw material testing, suggesting incomplete implementation of these guidelines.
  1. Export Bans and Blacklisting
  • Details: Following the Gambia and Uzbekistan incidents, India banned exports from implicated manufacturers (e.g., Maiden Pharmaceuticals, Marion Biotech) and blacklisted non-compliant firms from government tenders.
  • Impact: Strengthened accountability for exporters but highlighted the need for preemptive quality checks, as bans were reactive.

International Reforms and WHO Involvement

  1. WHO Alerts and Guidelines
  • Details: In October 2022, the World Health Organization (WHO) issued a global medical product alert for the contaminated Indian syrups, followed by updated guidelines in 2023:
    • Mandatory DEG/EG testing for glycerin and propylene glycol used in liquid medicines.
    • Recommendations for pharmacopoeia-compliant testing methods (e.g., gas chromatography) in all member states.
    • Strengthened Good Distribution Practices (GDP) to ensure supply chain integrity.
  • Impact: Prompted countries like Gambia, Indonesia, and Uzbekistan to enhance import controls and local testing. The WHO also facilitated training for regulators in low-resource settings.
  1. Global Pharmacopoeia Updates
  • Details: The United States Pharmacopeia (USP) and Indian Pharmacopoeia (IP) updated monographs in 2023 to include mandatory DEG/EG limits for excipients (e.g., <0.1% for glycerin). The International Council for Harmonisation (ICH) endorsed similar standards.
  • Impact: Standardized testing protocols globally, though adoption was slower in developing nations due to cost and infrastructure limitations.
  1. Country-Specific Responses
  • Gambia: Banned Indian cough syrup imports temporarily and established a national drug testing lab with WHO support.
  • Indonesia: Banned all liquid medicines for children in late 2022, later lifting the ban with stricter regulations on excipient testing and local production standards.
  • Uzbekistan: Suspended imports of Indian syrups and prosecuted local distributors, while upgrading its pharmacovigilance system.
  • Impact: These measures reduced immediate risks but exposed global reliance on Indian generics, necessitating long-term regulatory harmonization.

Gaps and Challenges Post-2022

Despite these reforms, the 2025 Madhya Pradesh Coldrif scandal (11-14 child deaths due to DEG-contaminated syrup) revealed persistent issues:

  • Domestic Market Oversight: While export regulations tightened, domestic drug quality control lagged, as seen with Sresan Pharmaceuticals’ failure to test Coldrif syrup.
  • State-Central Coordination: Decentralized regulation allowed lapses in Tamil Nadu, where Sresan operated, underscoring the need for centralized authority.
  • Supply Chain Vulnerabilities: Contaminated raw materials continued to enter production, indicating incomplete supplier audits.
  • Enforcement Gaps: Resource constraints and corruption in state drug control offices hindered consistent GMP enforcement.

Recent Developments (October 2025)

  • The Madhya Pradesh incident prompted the Union Health Ministry to announce a national video conference on cough syrup safety and expand risk-based inspections to all liquid formulation manufacturers.
  • Tamil Nadu, Kerala, and Uttarakhand banned Coldrif and similar syrups, with other states likely to follow.
  • The CDSCO is reviewing domestic testing protocols to align with export standards, potentially mandating DEG/EG testing for all cough syrups by late 2025.

Conclusion

Post-2022 Gambia, India introduced significant reforms, including mandatory DEG/EG testing for exports, stricter GMP enforcement, and risk-based inspections. However, the 2025 Coldrif scandal highlights that domestic regulation and supply chain oversight remain weak. Ongoing efforts to centralize drug regulation and harmonize global standards are critical to preventing future tragedies. For updates on 2025 reforms, monitor CDSCO or Union Health Ministry announcements.

Impact of Centralized Drug Regulation in India (Post-2022 Gambia Incident and 2025 Context)

Centralized drug regulation, where the Central Drugs Standard Control Organisation (CDSCO) would oversee licensing, quality control, and enforcement nationwide, has been proposed in India as a response to recurring pharmaceutical scandals, including the 2022 Gambia cough syrup deaths and the 2025 Madhya Pradesh Coldrif tragedy. While the proposal to amend the Drugs and Cosmetics Act, 1940, for centralized regulation was discussed in 2023, it remains under review as of October 2025. Below is an analysis of the potential and observed impacts of centralized drug regulation, drawing from post-2022 reforms and the current context.

Positive Impacts of Centralized Drug Regulation

  1. Uniform Standards and Enforcement
  • Impact: Centralization would replace India’s fragmented system, where 36 state drug controllers operate with varying resources and expertise. Uniform Good Manufacturing Practices (GMP) and testing protocols (e.g., for diethylene glycol [DEG] and ethylene glycol [EG]) would reduce discrepancies, as seen in the 2025 Coldrif case, where Tamil Nadu’s oversight failed to detect contamination.
  • Example: Post-2022, export-bound cough syrups required CDSCO-approved lab testing, reducing contamination risks abroad. Centralization could extend similar rigor to domestic markets, potentially preventing the 11-14 child deaths in Madhya Pradesh.
  1. Enhanced Accountability
  • Impact: A single regulatory authority would streamline accountability, reducing instances where state-level lapses (e.g., Sresan Pharmaceuticals’ untested Coldrif syrup) go unchecked. Centralized audits and licensing would deter non-compliance by manufacturers.
  • Example: The CDSCO’s 2023 risk-based inspections identified 25% of inspected firms as non-compliant, but state-level delays hindered action. Central control could expedite license suspensions or closures.
  1. Improved Supply Chain Oversight
  • Impact: Centralized regulation would enable better tracking of raw materials (e.g., glycerin, propylene glycol) across states, addressing the recurring issue of DEG contamination from unverified suppliers. A national database for supplier audits could prevent fraudulent substitutions.
  • Context: The 2022 Gambia and 2025 Madhya Pradesh incidents involved contaminated excipients, highlighting supply chain gaps that central oversight could address.
  1. Faster Response to Crises
  • Impact: A centralized CDSCO could issue nationwide bans, recalls, or testing mandates more quickly than state coordination allows. This would minimize delays, as seen in 2025 when Tamil Nadu, Kerala, and Uttarakhand issued separate bans on Coldrif syrup.
  • Example: Post-2022, the CDSCO’s export testing mandate was implemented swiftly, but domestic recalls relied on slower state action. Centralization could have accelerated the Coldrif ban.
  1. Global Reputation and Export Quality
  • Impact: Centralized regulation would align India’s domestic and export standards with international pharmacopoeias (e.g., USP, WHO), restoring trust in Indian pharmaceuticals after the 2022 Gambia and Uzbekistan scandals damaged its global reputation.
  • Data: India’s $50 billion pharmaceutical export industry faced scrutiny post-2022, with countries like Gambia banning imports. Centralized oversight could ensure consistent quality, boosting exports.
  1. Strengthened Pharmacovigilance
  • Impact: A national adverse drug reaction monitoring system under the CDSCO would improve detection of contamination cases, enabling quicker identification of issues like the 2025 Coldrif poisonings (48.6% DEG content).
  • Example: The WHO’s 2022 alert on Gambia prompted India to enhance pharmacovigilance for exports, but domestic monitoring lagged, contributing to the 2025 deaths.

Challenges and Negative Impacts

  1. Resistance from States
  • Impact: States like Tamil Nadu and Maharashtra, with large pharmaceutical industries, oppose centralization, fearing loss of revenue and autonomy. This has delayed the 2023 draft bill, stalling reforms as of October 2025.
  • Example: Tamil Nadu’s lax oversight of Sresan Pharmaceuticals in 2025 reflects state-level priorities that may resist CDSCO control.
  1. Resource Constraints
  • Impact: Centralizing regulation requires significant funding, infrastructure, and trained personnel. The CDSCO’s current staff of ~800 is inadequate for nationwide oversight, compared to India’s 10,000+ drug manufacturing units.
  • Context: Post-2022 inspections were limited by manpower, with only 200+ units audited by 2023. Scaling up could strain budgets, potentially leading to incomplete enforcement.
  1. Implementation Delays
  • Impact: Transitioning to a centralized system could disrupt existing state operations, causing delays in licensing and inspections. Small manufacturers, reliant on state approvals, might face closures if unable to meet stricter CDSCO standards.
  • Example: The 2023 GMP revisions led to temporary production halts for non-compliant firms, affecting drug availability. Centralization could amplify such disruptions.
  1. Risk of Bureaucratic Inefficiency
  • Impact: A centralized CDSCO could become bogged down by bureaucracy, slowing decision-making. Corruption risks, already a concern at the state level, could persist or worsen without robust checks.
  • Context: The 2025 Coldrif case exposed corruption allegations in Tamil Nadu’s drug approval process, suggesting that centralization alone may not eliminate malpractices.
  1. Impact on Small Manufacturers
  • Impact: Small and medium enterprises (SMEs), which dominate India’s pharmaceutical sector, may struggle to comply with centralized standards due to costlier testing and infrastructure upgrades. This could reduce competition and increase drug prices.
  • Data: SMEs account for ~40% of India’s drug production. Post-2022, many faced license suspensions for non-compliance, hinting at challenges under stricter central rules.

2025 Context: Madhya Pradesh Coldrif Scandal

The 2025 Coldrif scandal, where DEG-contaminated syrup killed 11-14 children, underscored the urgency of centralized regulation:

  • State-Level Failure: Tamil Nadu’s drug controller failed to detect DEG in Sresan Pharmaceuticals’ syrup, and Madhya Pradesh’s delayed response allowed continued prescriptions.
  • Central Response: The Union Health Ministry’s October 2025 call for nationwide inspections and a video conference on cough syrup safety reflects a push for centralized coordination, but the absence of a fully centralized system limited the response’s speed.
  • Public Demand: Outrage over the deaths, amplified by figures like Kamal Nath, has renewed calls for a single regulatory authority to prevent future lapses.

Observed Impacts from Partial Reforms

Post-2022, India’s partial centralization (e.g., CDSCO-led export testing) has had measurable effects:

  • Export Quality: Zero major DEG incidents in Indian exports since 2023, compared to Gambia and Uzbekistan in 2022.
  • Domestic Gaps: The 2025 Coldrif case shows that domestic markets still suffer from weak oversight, with 18 deaths across Madhya Pradesh and Rajasthan.
  • Inspection Scale: Risk-based inspections (2023-2025) covered only a fraction of manufacturers, missing firms like Sresan, which operated under state leniency.

Conclusion

Centralized drug regulation in India could significantly improve quality control, accountability, and crisis response, potentially preventing tragedies like the 2025 Coldrif scandal. However, challenges like state resistance, resource limitations, and risks to small manufacturers require careful management. The 2022 Gambia incident spurred export-focused reforms, but domestic gaps persist, as evidenced in 2025. Full centralization, if implemented by amending the Drugs and Cosmetics Act, could align India with global standards but demands robust funding and anti-corruption measures. For updates on the 2025 reform push, monitor CDSCO or Union Health Ministry announcements. If you need details on specific aspects (e.g., cost estimates, state objections), let me know!

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